Medical Conditions & Cannabis

Multiple sclerosis is an autoimmune disease that causes the body’s immune system to attack the central nervous system (CNS)–the brain and spinal cord.  The CNS is composed of neurons (nervous tissue cells) that communicate with each other, transmitting information throughout the brain and spinal cord.  These nerve cells create thought and perception and allow the brain to control the body.  MS causes the immune system to attack the protective, fatty coating called “myelin” that exists around the nerve cells and assists neurons in carrying electrical signals. This attack creates damaged areas or “lesions” within the CNS which inhibits the nerve cells from communicating as intended, resulting in CNS dysfunction.  MS inhibits proper signaling from one part of the brain to another—and from the brain to the rest of the body.  This impaired communication leads to changes in both cognitive and physical processes. MS is typically known to be “relapsing and remitting” also known as secondary progressive disease that may result in episodes of numbness, muscle weakness, dizziness, fatigue, changes in mobility, vision disturbances, changes in speech, and bowel and bladder dysfunction.  Another type of MS disease, “primary-progressive” is less common with similar symptoms but the disease course is different in that symptoms are consistent.  Regardless of the disease course, MS frequently results in not only pain but also in “spasticity”,  defined as a condition in which certain muscles are continuously contracted causing interference with normal movement, speech and gait.  You may read further information here, to learn more about MS.

Use of Medical Cannabis in MS

One recent study conducted by the National Multiple Sclerosis Society estimated that approximately 66% of MS suffers use cannabis to reduce their symptoms.¹  Other work reported on a reduction in opioid deaths indicating that cannabis has been substituted for opioids analgesics for use in pain, anxiety and sleep resulting in the reduction of accidental overdoses.  Following this logic, some patients have found they are able to decrease or eliminate their need for pharmaceuticals when including cannabinoids in their daily regimens.  Findings of several placebo-controlled studies through 2010, indicated that cannabinoids resulted in significant improvement in patient-reported spasticity with the combination of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Sativex, a balanced cannabis-based medicine (1:1 ratio containing 27 milligrams/ml, THC and  25mg/ml, CBD) for use in the treatment of neuropathic pain in Multiple Sclerosis, is approved in Great Britain and several other European countries.²    At this time THC and CBD have been found to benefit individuals with MS, particularly regarding pain and spasticity.

A recent review stated, “…the effects of cannabinoids on cells of the immune system, on the blood-brain barrier (BBB), microglia, astrocytes, oligodendrocytes and neurons, potentially open the way for a plethora of therapeutic actions on different targets that could aid the management of MS”.³  The multitude of potential therapeutic targets summarized by these authors may provide an indication as to why many MS patients find benefit with inclusion of cannabinoids in their daily regimens.  Many clinicians who work with cannabinoids and MS patients frequently recommend a 1:1 THC:CBD preparation, starting with a very low dose with slow, gradual upward titration to desired effect.

Cannabis and future MS research

There have been numerous pharmaceutical products developed and marketed over the past several years for MS, however, due to the toxicities associated with available pharmaceuticals, there has been increased interest in the use of cannabinoids for the management and treatment of MS.   Several pre-clinical studies (typically in animals or bench-research) have indicated the endocannabinoid system’s (ECS) key involvement with MS, including protection and preservation of the nervous system and repair or “re-myelination”.  It is anticipated this will be an important direction for future MS research—specifically to gain a better understanding of inflammatory mechanisms associated with neurological deterioration and repair.

FDA approved medications for MS

Currently, many medications developed by the pharmaceutical industry are identified as disease-modifying medicines yet many patients have issues with even the common adverse effects of the various regimens, ranging from injection site pain to fatigue, .  The term “disease-modifying” specifically indicates these medicines are able to limit the number of relapses, delay progression of the disability, and limit new disease activity (as seen on MRI).  A comprehensive listing of these medications is included here.  Additionally, an extensive listing of adjunctive pharmaceuticals used to address the symptoms of MS are also included.

References

¹ Kindred JH, Li K, Ketelhut NB, Proessl F, et al. Cannabis use in people with Parkinson’s disease and multiple sclerosis: a web-based investigation. Complement Ther Med. 2017; 33:99-104.

²  Rog DJ et al. Oromucosal δ9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension. Clinical Therapeutics. 2007, 29: 2068-2079.

³ Mecha M, et. al.,  Perspectives on Cannabis-Based Therapy of Multiple Sclerosis: A Mini-Review. Front Cell Neurosci (2020); 14:1-7. https://doi.org/10.3389/fncel. 2020; 34:1-7.

As of 2016, the Centers of Disease Control and Prevention estimated that about 2.4 million people in the US have chronic HCV.  Of patients acutely infected, approximately 75% progress to “chronic” HCV meaning the infection is present for greater than six months. The most common form of HCV accounts for 70-80% of the chronic HCV cases in the US.  Of those patients, about 20-30% are thought to progresses to cirrhosis which often takes decades to appear.  In some cases, liver cancers are caused by viral infections– some result from HCV-induced cirrhosis.  Due to the lengthy timeline for the effects of chronic HCV to manifest there are many tell-tale health issues that could serve to alert patients with this infection. Testing is important because symptoms may not develop until the HCV has resulted in extensive liver damage, possibly years after the initial infection.  To learn more about the risk factors, signs, symptoms and testing for HCV, you may click here.

Use of Medical Cannabis in HCV

Cannabis alone doesn’t treat the HCV infection, nor does it treat the complications that lead to liver disease and cirrhosis.  However, many people with HCV use cannabis to ease their general symptoms from the virus or to reduce the nausea associated with HCV pharmaceutical treatments.  Cannabis can be inhaled, taken as a pill, liquid or edible, or be absorbed under the tongue.  It’s unclear if there are any overall risks as research results have been mixed.  Cannabis does affect your liver and mostly has to do with the duration of HCV infection or “disease stage”.  In one study, using cannabis didn’t influence liver biopsies or show a negative effect with antiviral treatment so taking the drug didn’t interfere or further damage the liver. Furthermore, this study did not find any evidence that smoking or taking cannabis pills does any additional damage to the liver, despite what previous research had suggested. ¹

Some scientists have reported results from a few studies that credit marijuana use with stricter adherence to treatment protocols, due to reduced adverse drug effects experienced by the patient when using cannabis.  Researchers found that more people finished the full course of treatment and in turn, people experience better outcomes.  However, research in this area has also had mixed outcomes– Another study found that many HCV patients use cannabis routinely and that people who included the drug in their therapy plan didn’t necessarily stick to the plan more closely than their counterparts who didn’t take the drug.

Due to the complexity of cannabis’ effects on the liver, one should never attempt to self-manage HCV—Check with your cannabinoid doctor or pharmacist, if you think cannabis might be helpful to add to your treatment plan.

Cannabis and Future HCV Research

Due to the lack of effectiveness associated with cannabinoids in the treatment of HCV, there are no known clinical trials in this area.

FDA approved medications for HCV

Antiviral medications are typically a first line of defense against HCV.   Older products may give you flu-like symptoms and anemia.  Newer pharmaceuticals require shorter courses of therapy than more traditional therapies (from 24-72 weeks, now to 12 weeks) and have reduced adverse effects, however an associated risk is reactivation of the latent virus.  Most often pharmaceuticals will be prescribed for management of nausea and these drugs may be associated with their own adverse effects. 

 References

¹ Lui T, Howell GT, Turner L., et al., Marijuana use in hepatitis C infection does not affect liver biopsy histology or treatment outcomes. Can J Gastroenterol Hepatol 2014;28(7):381-384.

Crohn’s patients seek cannabinoid approvals because they have already found that it changes the course of their disease. After seeing the first several patients reporting marked improvement in their conditions with the use of cannabinoids other groups began reporting the same significant change.

All surveyed patients with Crohn’s disease report statistically significant improvement in signs and symptoms in all categories: pain in the gut, anorexia, nausea, vomiting, fatigue, depressed mood, and activity level. Based on a recent Israeli clinical study cannabinoids reduced pain in the gut more so than the pharmaceuticals that were provided. The number of stools per day was reduced, the body weight increased, and all patients reported the frequency and severity of flare-ups were reduced. Through the use of hemp many have seen these side effects reduce or completely become eliminated as the patient begins to embrace cannabinoid therapeutics.

It is now known that biopsy specimens from Crohn’s patients had large quantities of cannabinoid receptors. Activating these receptors with cannabinoids promoted healing of the gastrointestinal membrane. This could offer therapeutic relief to patients suffering from inflammatory disorders such as Crohn’s disease and ulcerative colitis.

Cannabinoid types of products that are available for Crohn’s disease patients credits raw cannabinoid juice, vaporizing and eating GMO free medible foods.

In the Summer of 1981, The Centers for Disease Control (CDC) first described the disease now known as acquired immune deficiency syndrome (AIDS).  AIDS was a significant contributor to illness and death in the United States for several years from the early-1980s to the mid-1990s and once better understood, the pathogen was identified as a human retrovirus then named HIV.  Due to the virus’ attack on the immune system, if gone untreated, the individual was left with extremely low defenses to combat several hallmark diseases, now associated with AIDS, including pneumocystis carinii pneumonia, and Kaposi’s sarcoma (a rare type of skin cancer).  Additional important complications of the disease include AIDS dementia, HIV neuropathy, wasting syndrome, nausea and vomiting associated with potent antiretroviral medications and depression.  You may review details about HIV/AIDS, its transmission, symptoms and associated infections, here

Use of Medical Cannabis in HIV/AIDS

In 2003, research confirmed that use of cannabinoids did not have a negative effect on HIV patients CD4 cell count or viral load (key indicators of patients’ HIV status)¹ From the very early days of the epidemic, cannabis was found to be effective in management of the numerous symptoms and complications of the infection or pharmaceutical therapy.  “Wasting syndrome” which involves profound, unexplained weight loss, is minimized with THC by stimulating the appetite of suffers.² Many patients also find cannabis helpful for AIDS-related neuropathic pain³ that may be caused by the virus, opportunistic infection, the antiviral regimen or a combination of these factors.  Researchers at UCLA recently published findings indicating that cannabis use in HIV patients is associated with a lower likelihood of cognitive decline than seen in HIV patients not using cannabis. Scientist speculate this may be due to the known anti-inflammatory effects of cannaboids.⁴  While newer drug regimens have reduced the severity of many of the associated complications of HIV, cannabis is still popularly embraced as a means to alleviate many adverse symptoms and complications that may accompany the infection and antiretroviral treatment.   Given the nature of these symptoms, both THC and CBD appear useful in the management of HIV/AIDS. As with other disease areas, patients should start with a low dose and titrate upward until desired effect(s) are achieved.

 Cannabis and Future HIV/AIDS Research

Therapies now available for the treatment of HIV/AIDS include pharmaceuticals that are used in various combinations or “cocktails”.  While therapeutic advances have been made that have resulted in HIV/AIDS becoming a more manageable, chronic infectious disease (from what was once thought to be a death sentence), the toxicities of these therapies are challenging for patients to endure. Cannabis has offered a source of relief for this population and important, well-designed research continues–such as evaluating cannabis ability to aid in opioid reduction in HIV adults experiencing generalized pain, cognition in a female and risk-reduction in adolescent populations, as well as a deeper dive into the effects of cannabis in HIV-neuropathic pain looking at specific dosing and extract concentrations.

 FDA approved medications for HIV/AIDS

Early HIV drugs were often associated with serious and debilitating side effects.  Currently, a multiple drug “cocktail” for the treatment of HIV is the standard of care in this infectious disease and appears to have effectively eradicated the virus (to where it is now considered a chronic disease), however, challenging toxicities continue such as nausea, vomiting, rash, fever, fatigue, headache, dizziness, headaches, diarrhea, loss of appetite, and neuropathic pain, to name a few of the most commonly experienced.  

 References

¹ Abrams, D. I., Hilton, J. F., Leiser, R. J., et al. (2003). Short-term effects of cannabinoids in patients with HIV-1 infection. A randomized, placebo-controlled clinical trial. Ann Intern Med, 139, 258-266.

² Haney, M., Gunderson, E. W., Rabkin, et. al. (2007). Dronabinol and marijuana in HIV-positive marijuana smokers. Caloric intake, mood, and sleep. J Acquir Immune Defic Syndr, 45(5), 545-554.

 ³ Ellis, R. J., Toperoff, W., Vaida, F., et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology, (2008) 34(3), 672-680.

⁴  Wei-Ming Watson, C.,  Paolillo, E, Morgan, E., et. al., Cannabis Exposure is Associated with a Lower Likelihood of Neurocognitive Impairment in People Living With  HIV. J Acquir Immune Defic Syndr (2019) 83(1):56-64

Glaucoma is a condition resulting in increased pressure within the eye. The pressure increase may cause damage to the internal blood vessels, nerve endings and may result in impaired vision with damage to the optic nerve. There are two basic types of glaucoma — chronic (open-angle glaucoma) and acute (closed-angle glaucoma).  In open-angle glaucoma, pressure slowly increases over time, often resulting in the loss of peripheral vision with difficulty seeing in the dark or driving at night. With acute, closed-angle glaucoma, the pupil becomes dilated and fixed which constitutes an medical emergency situation—immediate consultation with your physician is warranted and frequently surgery is required. The incidence of glaucoma increases with age and is also known to have a genetic component. Treatment for glaucoma typically includes use of a variety of medicated eyedrops.  For further information on glaucoma you may check here.

Use of Medical Cannabis in Glaucoma

First observed in 1971 during an investigation of healthy cannabis users, researchers noted that participants had reduced intraocular pressure (IOP).¹  It is noted that when taken intravenously, by smoking, or orally, IOP was reduced (but not when cannabis preparations were applied topically to the eye in the form of eye-drops).²  Cannabis decreases IOP by an average  of 25-30% and occasionally up to 50%. The specific mechanism in cannabis that causes this is not known.

Cannabis treatments for glaucoma have mostly been in combination with pharmaceutical eye drops, as the IOP lowering effects seem to be additive. In 1980, a non-psychoactive extract of cannabis was tested in combination with Timolol eye-drops in patients with high IOP. They found that the effects of the two medications were complementary and were beneficial in some cases where other medications had failed.

Formerly, it had been thought that inhalation of cannabis, as often as every three hours, was required to treat glaucoma and the ensuing side effects (euphoria) significantly outweighed the benefits, however, clinicians (and researchers) have now observed that with patients who use cannabis to treat glaucoma with chronic use, administration every 3 hours is not necessary for long-lasting eye pressure reduction. THC seems to be more effective than CBD,³ however, more testing is needed to determine how and when cannabinoids are best used in the treatment of glaucoma.

Cannabis and Future Glaucoma Research

At this time research with cannabinoids to address glaucoma is not an area of meaningful activity. x Active research has halted before the information required to support more robust decision-making has been elucidated.  The national organizations that provide support and resources for research have officially assumed the position that multiple, frequent dosing (smoking, typically)⁴ of THC is required for effectiveness in lowering IOP—although other research and clinical observation does not necessarily support this position.

FDA approved medications for Glaucoma

Currently, the medications developed by the pharmaceutical industry to treat glaucoma include several classes of drugs to allow use of multiple products should one product not be adequate to control the IOP–some of these products are available as combinations. These classes of drugs include prostaglandin analogs, beta blockers, alpha agonists, carbonic anhydrase inhibitors, and rho kinase inhibitors.  

References

¹ Hepler RS, Frank IR. Marihuana smoking and intraocular pressure. JAMA. 1971, 217: 1392.

² Tomida I, Pertwee RG, Azuara-Blanco A. Cannabinoids and glaucoma. Br J Ophthalmol. 2004, 88(5): 708-713.

³ Yazulla S. Endocannabinoids in the retina: From marijuana to neuroprotection. Prog Retin Eye Res. 2008, 27(5): 501-526.

⁴ Green K. The ocular effects of cannabinoids. Curr. Top. Eye Res. 1979, 1: 175–215.

Seizure Disorder is a broad term that is given to a variety of seizure-types, the most common of which is epilepsy.   Epilepsy is a chronic neurological brain disorder and is the fourth most common neurological disorder that affects both children and adults. A seizure is a brief change in brain activity associated with excessive electrical activation. An epilepsy diagnosis may occur with an individual after having had two or more seizures.  Epilepsy may occur as the result of a neurologic injury, infection, toxicity to the brain, or at times the cause may be unknown. A comprehensive summary of various types of seizures, disorders and syndromes including descriptions of their symptoms may be found here.

Use of Medical Cannabis in Seizure Disorder

While some patients will use cannabis to replace one or more of their pharmaceutical preparations, controlling seizures is serious and should always involve collaborative management by a Neurologist in conjunction with a cannabis expert.  Patients frequently note that the side-effects of anti-seizure pharmaceuticals are challenging and often, at the right dose and timing, may prefer cannabis due to reduced side effects.  It is key to remember to always be consistent with dose and timing of cannabis whether used alone or in conjunction with pharmaceutical preparations.  Due to the complexity of seizure disorders, one should always seek professional assistance with management, all the while keeping a journal of daily activities for optimal results.

While both THC and CBD are found to have anti-seizure activity, it is CBD (due to its non-euphoric activity) that has become the cannabis “go to” to address seizure disorder.¹  In June, 2019, the US-Food and Drug Administration (FDA) approved the first highly purified, plant derived CBD extract, called Epidiolex^®, for the treatment of two pediatric seizure conditions (Dravet’s Syndrome and Lennox-Gastaut syndrome).²  In conjunction with this approval, the Drug Enforcement Agency (DEA) changed the legal status of Epidiolex^® by moving it from a Schedule 1 drug (meaning it has no medical value) to a Schedule 5 drug (the lowest/most relaxed classification under the Controlled Substances Act). Many states in the US now allow the use of CBD-rich cannabis due to the activism of parents with children with epilepsy who want access.

It is important to note that the origin and processing of the cannabis preparation is important. With highly purified products, many valuable anti-seizure constituents are removed during this activity. Not only are the cannabinoids (CBD or THC) anticonvulsant, but the terpenes in a full cannabis extract may increase effectiveness. In one study of 272 patients, 86% had some degree of seizure reduction while using whole-plant cannabis.

Utilizing cannabis for seizure control requires professional advice and active involvement. One may also use cannabis to help with control of symptoms, like agitation, insomnia or as a general antioxidant. One should never attempt to self-manage in this situation. If used for seizure control, most protocols involve high doses of CBD-rich cannabis.  Most often the CBD will be supplied as an oil concentrate or tincture. Dosing of children is calculated by body weight and given in divided daily doses (typically 3 times daily). Adults may take very large daily doses, as well.  CBD used for anxiety/agitation associated with seizure disorders requires far lower doses (10 to 25 mg/dose).

 Cannabis and Future Seizure Disorder Research

The interest in cannabis preparations in the treatment of seizures, particularly drug refractory childhood epilepsies, has sky-rocketed in recent years.  With over 120 phytocannabinoids known to scientist’s,  look for research on a couple important lesser known cannabinoid options: THCA (a non-euphoric precursor to THC) and CBDV which is structurally similar to CBD,  and is also not intoxicating when isolated.⁴

FDA approved medications for Seizure Disorder

Currently, the primary treatment approach for epilepsy are anti-seizure medications developed by the pharmaceutical industry.  Many of these have challenging side-effects and often two or three medications are required to adequately quell the seizure activity. The typical course of epilepsy is often marked with remission that may include periods of two to five years without a seizure. This may occur while the patient is taking an anti-seizure medicine as well as when the medicine is withdrawn.

Also, sometimes useful in seizure regulation is a ketogenic diet, and control of post-seizure symptoms which may include “brain-fog”,  fatigue, and mood-disturbances, addressed by counseling and/or medications. A last resort for seizure control is brain surgery or nerve stimulation.

References

¹ Ames FR, Cridland S. Anticonvulsant effect of cannabidiol. South African Medical Journal. 1985, 69: 14.

² Morano A., et. al., Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects. Neurotherapeutics 2015, 12:747–768 DOI 10.1007/s13311-015-0375-5.

⁴ Perucca E., Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?  J Epilepsy Research. 2017, 7: 2.

Autism spectrum disorder (ASD) is a neurodevelopment disorder that manifests as a developmental disability  that can cause significant social, communication and behavioral challenges. Typically, nothing about the physical appearance of persons with ASD sets them apart from others. Those with ASD often communicate, learn, and problem-solve differently and their abilities may range from gifted to severely challenged. Some people with ASD need a lot of help in their daily lives; others need less.  The US Center for Disease Control has indicated the numbers of children diagnosed with ASD (primarily boys) has steadily increased over recent years with the impact in 2000 noted to be 1 in 150, and 2014 1 in 59.  Several explanations for this phenomenon exist, however, as scientists do not fully understand the complex, causative factors involved in the development of ASD, some speculate one reason may be a change in diagnostic criteria.

A diagnosis of ASD now includes several conditions that used to be diagnosed separately including autistic disorder, pervasive developmental disorder and Asperger syndrome. These conditions are now all called ASD.  To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD.  The major characteristics of autism fall in four main areas: impaired social skills, delayed or disordered speech, limits in the range of interests and repetitive behaviors—all of these areas implicate an imbalance in the endocannabinoid system which is involved in their modulation. Most often these impairments are noted in early childhood and last throughout life.  Approximately 20-30% (some sources report a greater %) of patients with autism also have seizure disorder.  For more information on ASD, its symptoms, diagnosis and screening, you may read more here.

Use of Medical Cannabis in ASD

Since the early 2000s, anecdotes have emerged from the community as to the usefulness of cannabinoids in aiding the management of ASD symptoms.  There is not one clear approach in this group: THC vs CBD vs THCA.  It is still very early and unclear as to the most effective type of preparation, including specific cannabinoids and ratios.  A variety of observational research (not placebo controlled, not allowing conclusions to be developed from resulting information) has been conducted using synthetics as well as naturally occurring cannabinoids.  For example, reported in 2019, 180 ASD patients were treated with 20:1, CBD:THC (CBD rich) and results were reported upon by a group of prominent Israeli scientists. The findings concluded that after 6 months of treatment, approximately 80% of patients experienced a significant or moderate improvement.¹  Eleven of the 13 ASD patients who also experienced seizures, reported a complete disappearance of symptoms, while the remaining two patients reported improvement.  Approximately 13% (23 patients) reported adverse side effects such as sleepiness, restlessness, psychoactive effects, increased appetite and dry mouth. Ultimately, researchers concluded: “Cannabis as a treatment in ASD patients appears to be well-tolerated, safe and seemingly effective option to relieve symptoms, mainly: seizures, tics, depression, restlessness and rage attacks.”  Another recent study (2019) reported similar positive findings.  With this said,  high ratio, CBD-rich cannabis preparations have resulted in positive outcomes in the treatment of symptoms typically experienced by ASD patients in other studies, as well.  While these studies hold promise for families with members who suffer from ASD,  they remain observational as they are not placebo controlled. Most of the information available for the treatment and management of autism related symptoms is due to observational research— However, parents of some autistic children report that cannabis eases behavioral problems more effectively than conventional pharmaceuticals, without the adverse effects noted with pharmaceutical agents.   Regardless of chosen cannabinoids, the strategy should always be very low-dose initiation with slow upward titration (gradual increases in dose) to desired effects.

 Cannabis and Future ASD Research

Several early, proof of concept studies were conducted with dronabinol, a synthetic THC.  Subsequently, there are currently numerous clinical trials outside of the US (Israel, Australia, Chile) that are either in planning or underway using cannabis to treat autism.  An summary describing several new and ongoing studies may be found here.

FDA approved approaches for the management of ASD symptoms

Currently the only available pharmaceutical indicated for ASD patients is riluzole, a drug originally developed for amyotrophic lateral sclerosis (ALS).  The research study was completed in 2012 with a stated purpose of treating children and adolescents (with or without ASD) who have  obsessive-compulsive disorder.  

Riluzole, is involved with neuronal signaling and is viewed by many as having limited therapeutic value.² Other medications frequently used in symptom management include pharmaceuticals such as antiepileptics, antidepressants, anxiolytics, antipsychotics, mood stabilizers and muscle relaxers.  Also currently employed for management are a variety of  behavior, communication approaches, and dietary interventions.

References

¹  Bar-Lev Schleider L, Mechoulam R, et.al., Real life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy. Nature/Scientific Reports (2019) 9:200 | DOI:10.1038/s41598-018-37570-y

 ² Wink LK, et. al. A Randomized Placebo-Controlled Cross-Over Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorder.  J Autism Dev Disord. 2018 Sep;48(9):3051-3060. doi: 10.1007/s10803-018-3562-5.

Research has shown that cannabis helps slow the progression of Huntington’s disease through its interaction with the endocannabinoid system. After studies determined that Huntington’s disease was related to a loss of cannabinoid receptors in the basal ganglia, researchers set out to examine whether increasing endocannabinoid activity could be therapeutically beneficial for treating the disease. Results have been encouraging.

In preclinical trials, the major cannabinoids found in cannabis have been found to be effective at protecting the life of neurons in the brain. Research has shown that through the activation of cannabinoid 2 receptors (CB₂), the inflammation and toxicity of microglial cells is reduced, which in turn slows the neurodegeneration caused by Huntington’s disease². Through the activation of cannabinoid 1 receptors (CB₁), cannabinoids have shown to effectively alleviate specific motor symptoms like tremors and movement disorders and reduce the process in which neurons are damaged and killed to slow the progression of the disease.

Additionally, studies examining the effect of cannabis-based medications on Huntington’s disease have proven cannabinoids effective at delaying the progression of the disorder.

Researchers suggest that targeting the cannabinoid system with cannabinoids may have a potential therapeutic benefit for treating basal ganglia disorders like Parkinson’s disease and Huntington’s disease. Cannabinoids are effective at providing neuroprotection through three methods: reducing inflammation by activating CB₂ receptors, limiting cell death by activating CB₁ receptors, and providing an antioxidant effect through a mechanism independent of cannabinoid receptors. Studies also indicate that cannabinoids are effective at reducing muscle spasms and the inability to concentrate through their direct activation of vanilloid TRPV(1) receptors.

Severe nausea may occur for a variety of reasons and may be a brief episode or remain ongoing and may occur with or without vomiting.  Brief intermittent episodes might be due to pain, stress, overeating, excess alcohol, motion sickness or a reaction to medications. Chronic, severe nausea will typically be the result of infection, liver disorders, food poisoning, pregnancy or possibly brain abnormalities. Additionally, severe nausea often accompanies some cancers, typically in conjunction with chemotherapy. Nausea with vomiting is more likely to occur with food reactions, infection, or when food stops moving through the GI tract. Also, patients may experience Cannabis Hyperemesis Syndrome (CHS). Chronic (typically high dose) cannabis use may result in CHS that causes severe vomiting.  This is a rare condition and paradoxical in nature as cannabis has been used since ancient times for it’s antiemetic (nausea treatment) properties.

Use of Medical Cannabis in Severe Nausea

Our  stomach and GI contain many endocannabinoid receptors that are naturally occurring and are involved in the regulation of nausea and vomiting in humans (as well as other animals).¹  In the late 1970s/early 1980s, inadequate treatment of chemotherapy-induced nausea and vomiting led researchers to seek alternatives to the pharmaceutical products that were in use at the time.  These investigations resulted in the 1985 approval and marketing of a synthetic Δ9-Tetrahydrocannabinol (THC) product dronabinol (Marinol^®),  for the treatment of nausea and vomiting associated with chemotherapy.²  Synthetic THCs effects have been confirmed in a double-blind, placebo-controlled trial versus a strong pharmaceutical antiemetics.  Many patients experience adverse effects with the synthetic THC drug and prefer the effects of cannabis.

While THC is associated with very good effectiveness for use in nausea, cannabidiol (CBD) (in animal models) also suppresses nausea and vomiting within a more limited dose range.  Sativex^® is a prescription product approved for use outside the US, with an approximate 1:1 ratio of CBD:THC, has also been found to decrease chemotherapy-induced nausea and vomiting in preclinical trials.

One must consider the nausea (and possible vomiting) that may occur and select the best approach for administering cannabis under these circumstances.  For this purpose, the preferred methods of cannabis delivery include the use of inhaled, or sublingual (under the tongue) products. Doses of 5-10 mg are usually effective, or alternatively, 1-2 puffs of a smoked or vaporized product.

Cannabis and Future Nausea Research

Currently, cannabis research focused on nausea (with or without vomiting) is not a priority, likely because of its long history of use and that it is established as a good choice for the management of this issue.

FDA approved medications for Nausea

Currently, the medications developed by the pharmaceutical industry to treat nausea include a variety of classes/types of drugs, prescribed dependent upon the underlying cause of the nausea.  For example, frequently antihistamines will be prescribed for motion sickness.  For post-surgery, a serotonin or dopamine receptor-blocker or even corticosteroid may be prescribed.  There are several pharmaceutical options available for the treatment of nausea—typically having adverse effects and potential complications.  More information may be learned about these options and consequent side-effects here.

References

¹ Parker LA, Rock EM, Limebeer CL. Regulation of nausea and vomiting by cannabinoids. Br J Pharmacol. 2011, 163(7):1411-22.

²Meiri E, et al. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin. 2007, 23: 533-543.

What is the science and pharmacology behind marijuana, and can it be used to treat Parkinson’s symptoms?

The endocannabinoid system is located in the brain and made up of cannabinoid receptors (a receptor is molecular switch on the outside of a cell that makes something happen inside a cell when activated) that are linked to neurons (brain cells) that regulate thinking and some body functions.

Researchers began to show enthusiasm to study cannabis in relation to PD after people with PD gave anecdotal reports and posted on social media as to how cannabis allegedly reduced their tremors. Some researchers think that cannabis might be neuroprotective — saving neurons from damage caused by PD.

Cannabinoids (the drug molecules in marijuana) have also been studied for use in treating other symptoms, like bradykinesia (slowness caused by PD) and dyskinesia (excess movement caused by levodopa). Despite some promising preclinical findings, researchers have not found any meaningful or conclusive benefits of cannabis for people with PD.

Researchers issue caution for people with PD who use cannabis because of its effect on thinking. PD can impair the executive function — the ability to make plans and limit risky behavior. People with a medical condition that impairs executive function should be cautious about using any medication that can compound this effect.