A Role for Medical Cannabis in Combating the Opioid Epidemic

Drug overdoses and opioid-related deaths have reached epidemic proportions throughout the United States (1). Over the past 25 years or so, the number of opioid-related deaths (from prescription opioids including oxycodone, hydrocodone and methadone and heroin) quadrupled to more than 200,000 (2). In 2015 alone, opioid overdoses resulted in 33,901deaths (1, 2) and in 2016 nearly half of all opioid-related deaths involved prescription opioids (CDC). Today, opioid-related deaths in the US surpass combined deaths caused by both car accidents and guns annually (2, 3).

Cause of the Epidemic

While the exact causes of the current opioid academic are uncertain, a variety of factors including job loss, chronic unemployment, financial hardship and over-marketing/over-prescribing of opioids have been suggested. It is important to note, however that between 1981 and 2011 the number of opioid prescriptions in the US tripled from 76 million to 219 million per year (4). According to a recent survey, over 97 million people took prescription opioids in 2015 and of these, roughly 12 million used opioids without being directed by a doctor (5).  Interestingly, because of recent state legislative initiatives that restrict the opioid prescribing habits of physicians, the number prescription opioids deaths appeared to level off in 2011(6). However, since 2011 the number of heroin overdose deaths and those related to illegal “black market” synthetic opioids like fentanyl has skyrocketed (CDC) in many hard hit states like West Virginia, Pennsylvania and New Hampshire. This is because heroin and fentanyl are now much cheaper and more available than prescription opioids (6).

The current opioid epidemic is forcing many physicians to reevaluate their use of prescription opioids for pain control and to consider alternative pain management strategies. There is an emerging body of evidence that suggests that medical cannabis (smoked, vaporized or ingested) can effectively manage and control chronic non-cancer pain (6-9), reduce opioid consumption (10-15) and help to lower opioid overdose deaths (14, 15).

Medical Cannabis and Pain Management

There are numerous reports that show that smoked or vaporized medical marijuana (and cannabis extracts), used alone or in combination with opioids, can effectively treat chronic neuropathic pain, muscle pain associated with spasticity from Multiple Sclerosis and certain types of cancer pain (8,9). More important, these studies found that smoked/vaporized cannabis or its extracts induce few adverse side effects and are safe for use; even in chronic pain patients who take prescription opioids for pain management (7).

Cannabis Reduces Opioid Consumption and Lowers Overdose Deaths

Although cannabis is not approved as a treatment for pain in the US, there is new evidence from states where medical cannabis is legal that cannabis reduces opioid consumption in chronic pain patients. Several studies in the US and around the world showed that opioid use dropped by as much as 50% among chronic pain patients when they were given access to cannabis. (10, 11). Further, other studies with chronic pain patients showed that cannabis use—along with its opioid-sparring effect—enhanced patient executive cognitive performance (12). The observed improved cognitive functioning likely resulted from a 42% reduction in opioid use by these patients (12).

A study that researched the association between the existence of state medical marijuana laws and opioid overdose deaths from 1999 to 2010 found that opioid overdose deaths declined by as much as 25% in states that had medical cannabis laws in effect (14). Other research showed that reductions in opioid overdose deaths tend to improve in states where medical cannabis laws have been in effect the longest (15). For example, in California, where medical cannabis laws have been in effect since 1996, there has been a 33% drop in the number of opioid overdose deaths (14). Similar reductions were also observed in other legacy medical cannabis states such as Oregon, Colorado and the State of Washington (14,15).

Other Efforts

Several biotechnology and pharmaceutical companies are attempting to develop cannabis –derived drugs and mimetics that treat pain by binding to certain types of cannabis receptors found throughout the body (16). Removing cannabis’ psychotropic effects and preserving its pain-relieving benefits is the major objective for this new class of drugs (16). Although these drugs are still in early stages of development, using them rather than addictive opioids to manage chronic pain would be an important step in curbing opioid overuse and abuse.

A Path Forward

Physicians play a critical role in prescription drug misuse and abuse prevention. To that point, continuing medical education programs that help raise awareness and educate physicians about the benefits of cannabis for pain management represents and important first step to curb over-prescription of opioids. Further, ongoing political and financial support for recent federal initiatives (17) such as enhancing access to prescription drug monitoring using health information technology, formalized collaborative efforts between insurers, health care providers, and employers to combat opioid misuse and abuse and community-based programs like the national take-back initiative—which provides a safe, secure, environmentally-responsible plan for disposing of prescription opioids and educates the public about the potential for abusing and trafficking prescription medications—will also be critical. Finally, new federal and state legislation that offers counseling and medical solutions to treat opioid abusers rather than punish them will be vital to control America’s epidemic opioid crisis.

References

  1. Rudd RA, Seth P, David F, Scholl L. Increases in Drug and opioid-involved overdose deaths — United States, 2010–2015. MMWR Morb Mortal Wkly Rep. ePub: 16 December 2016. DOI: http://dx.doi.org/10.15585/mmwr.mm6550e1  Accessed October 23, 2017
  2. CDC. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2016. Available at http://wonder.cdc.gov  Accessed October 23, 2017.
  3. Drug overdoes now kill more Americans than guns. CBS News 2016 https://www.cbsnews.com/news/drug-overdose-deaths-heroin-opioid-prescription-painkillers-more-than-guns/ Accessed October 23, 2017
  4. America’s opioid epidemic is worsening. The Economist (UK) 2017    https://www.economist.com/blogs/graphicdetail/2017/03/daily-chart-3  Accessed  October 23, 2017.
  5. Hughes A, William MR, Lipari RN, Bose J. Prescription drug use and misuse in the United States: results from the 2015 national survey on drug use and health. Substance Abuse and Mental Health Services Administration (SAMHSA) 2016 https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR2-2015/NSDUH-FFR2-2015.htm  Accessed October 23, 2017.
  6. Katz J. Short answers to hard questions about the opioid crisis. The New York Times 20 https://www.nytimes.com/interactive/2017/08/03/upshot/opioid-drug-overdose-epidemic.html Accessed October 23, 2017.
  7. Jensen B, Chen J, Furnish T, Wallace M. Medical marijuana and chronic pain: a review of basic science and clinical evidence. Curr Pain Headache Rep. 2015; 19:50 doi: 10.1007/s11916-015-0524-x.
  8. Wilsey B, Marcotte, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. J. Pain. 2013; 14:136-148.
  9. Andreae MH, Carter GM, Shaparin N, Suslov K, et al. Inhaled cannabis for chronic neuropathic pain: a meta-analysis of individual patient data J. Pain 2015; 16:1221-1232.
  10. Boehnke KF, Litinas E, Clauw DJ. Medical cannabis use is associated with decreased opiate medication: use in a retrospective cross-sectional survey of patients with chronic pain. J Pain. 2016; 17:739-744.
  11. Haroutounian S, Ratz Y, Ginosar Y, Furmanov K, Saifi F, Meidan R, Davidson E. The effect of medicinal cannabis on pain and quality-of-life outcomes in chronic pain: A prospective open-label study. Clin J Pain. 2016; 32:1036-1043
  12. Gruber SA, Sagar KA, Dahlgren MK, Racine MT, Smith RT, Lukas SE. Splendor in the Grass? A pilot study assessing the impact of medical marijuana on executive function. Front Pharmacol. 2016; 7: 355  eCollection 2016.
  13. Bradford AC, Bradford WD. Medical marijuana laws reduce prescription medication use in Medicare Part D. Health Aff (Millwood). 2016; 35:1230-1236.
  14. Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA. Intern Med. 2014; 174:1668-1673.
  15. Kim JH, Santaella-Tenorio J, Mauro C, Wrobel J, Cerda M, Keyes KM, Hasin D, Martins SS, Li G. State medical marijuana laws and the prevalence of opioids detected among fatally injured drivers. Am J Public Health. 2016; 106: 2032-2037.
  16. Mintz CS, Fabrizio AJ, Nison E. Cannabis-Derived Pharmaceuticals. J. Comm. Biotechnol. 2015; 21:16-30.
  17. SAMHSA’s effort to fight prescription drug misuse and abuse. https://www.samhsa.gov/prescription-drug-misuse-abuse/samhsas-effort  Accessed October 23, 2017.

Cannabis and Its Effect on High Blood Pressure

According to recent estimates, about 75 million American adults have has high blood pressure (1), a condition commonly referred to as hypertension. If untreated, it can lead to cardiovascular disease, which is characterized by an increased risk of stroke, heart attack, and even heart failure. Hypertension was the cause of over 400,000 deaths in 2014 (1).

A number of factors, including poor diet, stress, physical inactivity, alcohol, and tobacco use increase the risk of developing hypertension (1). Hypertension can be managed by taking medications, reducing sodium in the diet, getting daily physical activity, and quitting smoking (2).

Previous reports suggest that consumption of cannabis and certain cannabinoids e.g, cannabidiol (CBD) may help to lower high blood pressure and represent a new treatment option for hypertension (3-5).   Further, results from a 15 year longitudinal study called the Coronary Risk Development in Young Adults (CARDIA) which followed 3,617 black and white young adults suggested that cannabis consumption was not independently associated with increased cardiovascular risk (6). However, study authors cautioned that it was associated with unhealthy behaviors including high caloric diet, tobacco smoking and other illegal drug use.

In a more recent retrospective analysis of 1213 young adults (20 years and older)—57% used cannabis—Yankey et al. (7) showed that cannabis use may increase the risk of death from hypertension. Study results suggested that cannabis users had more than three times the risk of death from hypertension-related causes. Moreover, increased duration of cannabis use was also associated with a greater risk of death from hypertension. However, it is important to note that the researchers acknowledged the difficulty of measuring frequency and quantities of marijuana used by study participants and the likelihood that illegal use was underreported (7). Put simply, there are confounding variables that call into question the conclusions of the study.

In summary, the positive or negative effects of cannabis consumption on cardiovascular health and disease still remain to be conclusively determined. New well designed and better controlled clinical studies will be necessary to verify or refute the effects of cannabis and cannabinoids on cardiovascular function and their ability to manage hypertension.

References

  1. https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_bloodpressure.htm  Accessed August 23, 2017
  2. http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/high-blood-pressure/art-20046974  Accessed August 23, 2017
  3. Pacher P, Batkal S, Kunos G. Cardiovascular pharmacology of cannabinoids. Handb Exp Pharmacol 2005; 168:599-625
  4. Randall MD, Harris D, Kendall DA, Ralevic V. Cardiovascular effects of cannabinoids. Pharmacol Ther. 2002;95:191–202.
  5. Hiley CR, Ford WR. Cannabinoid pharmacology in the cardiovascular system: potential protective mechanisms through lipid signalling. Biol Rev Camb Philos Soc. 2004;79:187–205
  6. Rodondi N, Pletcher MJ, Liu K, Hulley SB, Sidney S  Marijuana use, diet, body mass index and cardiovascular risk factors (from the CARDIA study). Am J Cardiol 2006; 98:478-484
  7. Yankey B, Rothenberg R, Strasser S, Ramsey-White K, Okosun IS Effect of marijuana use on cardiovascular and cerebrovascular mortality: A new study using the National Health and Nutrition Survey linked mortality file. Eur J Preventive Cardiol 2017; DOI: 10.1177/2047487317723212 [Epub ahead of print]

Cannabis and Post-Traumatic Stress Syndrome: It’s Complicated

There is growing anecdotal evidence that cannabis and certain phytocannabinoids may be helpful when treating persons suffering from post-traumatic stress syndrome (PTSD).  For those who may not know, PTSD is a state of mind activated by either witnessing or experiencing a shocking, frightening or horrifying episode. Many war veterans as well as sexual assault victims and others may experience PTSD at some point in their lives. At present, PTSD is a qualifying medical condition in most states where medical cannabis is legal (1).

While cannabis is fast becoming the “go to” treatment for patients with PTSD, there is currently a dearth of scientific evidence to support its effectiveness. To that point, the results from a retrospective analysis showed that only 1 in 5 studies involving cannabis and PTSD showed a small but statistically meaningful decline in PTSD symptoms for patients who used cannabis (2). Moreover, older studies suggested that cannabis use may reduce the effectiveness of conventional treatments for PTSD and may be associated with poorer clinical outcomes (1, 3).

While there is conflicting evidence about the effectiveness of cannabis as a treatment for PTSD, there is general agreement among PTSD researchers that there have not been enough controlled clinical studies to provide conclusive evidence about the benefits or harm of plant-based cannabis preparations as PTSD treatments (4). At present there are two ongoing randomized trials and 6 other studies examining outcomes of cannabis use in patients with PTSD (4). These studies are expected to be completed within 3 years.

By then, there will hopefully be a conclusive answer!

References

  1. Wilkinson ST, Stefanovics E, Rosenheck RA. Marijuana use is associated with worse outcomes in symptom severity and violent behavior in patients with posttraumatic stress disorder. J Clin Psychiatry. 2015 Sep; 76(9): 1174-80.
  2. https://www.reuters.com/article/us-health-cannabis-pain-ptsd-idUSKCN1AU2DG  Accessed August 16, 2017
  3. Manhapra A, Stefanovics E, Rosenheck R. Treatment outcomes for veterans with PTSD and substance use: Impact of specific substances and achievement of abstinence. Drug Alcohol Depend. 2015 Sep 25. pii: S0376-8716(15)01664-6. [Epub ahead of print]
  4. http://annals.org/aim/article/2648596/benefits-harms-plant-based-cannabis-posttraumatic-stress-disorder-systematic-review  Accessed August 16, 2017

Cannabidiol (CBD) and Opioid Addiction

Opioids provide effective analgesic relief against acute and chronic pain.  Rates of opioid prescription have skyrocketed over the past two decades and opioid addiction is extremely high among users reaching almost 50% (1, 2).  As opioid prescription and addiction rates rise, overdose deaths in the US have nearly tripled in the past 15 years (3).

Cannabidiol (CBD) is a non-psychoactive cannabinoid that has been reported to dampen the “reward properties” of drugs like cocaine, amphetamine and opioids in animal models (4, 5). Put simply, CBD might be able to block the urge of users to continue to use these highly addictive drugs.

In a recent study conducted at the University of Mississippi, Markos et al (6) injected separate groups of mice with either saline (control) or morphine in combination with different doses of CBD. The treated mice were then subjected to drug/no drug conditioning experiments.  The results from these experiments showed that morphine-conditioned mice displayed a robust preference for morphine. This robust morphine preference was significantly attenuated in mice that also received morphine plus CBD (10 mg/kg). Further, CBD (10 mg/kg) alone did not exhibit any rewarding or aversive properties in saline-conditioned mice. This finding is the consistent with the work of others who also found that CBD lacks psychotomimetic, aversive or reward properties (7-10).

Taken together, these results suggest CBD can block opioid reward behavior, i.e. deter the subsequent use of opioids, and may be useful as a treatment in opioid addiction treatment settings.  However, while these results may be encouraging, controlled, human clinical studies with CBD must be performed to determine whether or not the cannabinoid may be useful as a pharmacologic intervention to help treat opioid addiction.

References

  1. Dart RC, Surratt HL, Cicero TJ, Parrino MW, Severtson SG, Bucher-Bartelson B, Green JL. Trends in opioid analgesic abuse and mortality in the United States. N Engl J Med 2015; 372: 241–248
  2. Højsted J, Sjøgren P. Addiction to opioids in chronic pain patients: a literature review. Eur J Pain 2007; 11: 490–518
  3. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths – United States, 2010–2015. MMWR Morb Mortal Wkly Rep 2016; 65: 1445–1452
  4. Parker L, Burton P, Sorge R, Yakiwchuk C, Mechoulam R. Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmachology 2004; 175: 360–366
  5. Katsidoni V, Anagnostou I, Panagis G. Cannabidiol inhibits the reward facilitating effect of morphine: involvement of 5-HT1A receptors in the dorsal raphe nucleus. Addict Biol 2013; 18: 286–296
  6. Markos JR, Harris HM, Gul W, ElSohly MA, Sufka KJ.  Effects of cannabidiol on morphine conditioned place preference in mice. Planta Med 2017 12/13 DOI: 10.1055/s-0043-117838
  7. Parker L, Burton P, Sorge R, Yakiwchuk C, Mechoulam R. Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmachology 2004; 175: 360–366
  8. Katsidoni V, Anagnostou I, Panagis G. Cannabidiol inhibits the reward facilitating effect of morphine: involvement of 5-HT1A receptors in the dorsal raphe nucleus. Addict Biol 2013; 18: 286–296
  9. Mechoulam R, Parker L, Gallily R. Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol 2002; 42: 11S‑19S
  10. Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus L. Cannabidiol – recent advances. Chem Biodivers 2007; 4: 1678–1692

THC, CBD and Multiple Sclerosis

The established immunomodulatory properties of certain cannabinoids, most notably Δ-9 tetrahydrocannabinol (THC)  and cannabidiol (CBD), suggested that they may be therapeutically useful to treat multiple sclerosis (MS) which is generally believed to be autoimmune neurological diseases. (1). To that point, from 2005-2009, clinical trials involving 1300 patients were conducted to assess the effects of Cannabis, cannabis extracts and synthetic THC on MS and MS-related muscle spasticity and pain. (2, 3).

The results of these studies showed that cannabis extracts containing different ratios of THC and CBD as well as THC and nabilone (synthetic THC) can improve MS-related symptoms of spasticity, pain and urinary incontinence.  (2, 3 ) Additional clinical studies led to the approval of GW Pharma’s Sativex® (1:1 ratio of THC: CBD) in 27 countries (not the US) as a treatment for MS spasticity (4).

At present, in the US, there are 15 late stage clinical trials in progress that are evaluating smoked/vaporized cannabis (2) and Sativex® (13) as treatments for MS and MS-related spasticity, pain and urinary incontinence (Table 1).

Based on GW Pharma’s success with Sativex® as a treatment for various MS indications in other countries, it is likely the company will receive approval as an MS treatment in the US.

 References

  1. Giacoppo S, Mandolino G, Galuppo M, Bramanti P, Mazzon E. Cannabinoids: new promising agents in the treatment of neurological diseases. Molecules 2014; 19:18781-18816
  2. Zajicek JP, Apostu VI. Role of cannabinoids in multiple sclerosis. CNS Drugs 2011; 25:187-201
  3. Hazenkamp A GF. (2010) Review on clinical studies with cannabis and cannabinoids 2005-2009. Cannabinoids 5(special issue) 2010; 1-21.
  4. Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG, Group MR. (2012) Multiple sclerosis and extract of cannabis: results of the MUSEC trial. Journal of Neurology, Neurosurgery, and Psychiatry 2012; 83:1125-1132.

Cannabis Extracts, Cannabinoids and Cancer Treatment

There is a growing body of evidence that cannabinoids may have anti-tumor and cancer–fighting effects (1, 2).

Numerous studies have demonstrated inhibition of tumor growth in vitro and in animal models of disease for a variety of cancers including glioblastoma, breast, prostate, thyroid, colon, skin, pancreatic, leukemia and lymphoma (3).

The exact mechanism by which cannabinoids exert their anti-tumor effects is thought to occur via suppression of proliferative cell signaling pathways, inhibition of angiogenesis (blood vessel formation) and cell migration, stimulation of apoptosis (programmed cell death) and induction of autophagy (intracellular degradation) [3, 4].  Interestingly, cannabinoid receptors CB1 and CB2 have been found in higher concentrations on tumor cells than on surrounding normal tissue for a variety of cancers (5, 6).  Also, several studies suggest that cannabinoids may selectively inhibit tumor cell growth and proliferation while sparing normal tissue (3, 7).

Although cannabinoids exhibit possible anti-tumor effects, only a single Phase 1  clinical trial that assessed the safety and efficacy of THC in 9 patients with treatment refractory glioblastoma multiforme has been published (8).

However, at present, there are only two Phase 2 clinical trials underway or completed to assess the effect of cannabis extracts on solid tumor growth (NCT02255292) and glioblastoma (NCT01812603).  Clearly, more clinical studies are necessary to determine whether or not Cannabis extracts or different cannabinoids (singly or in combination) can be used as safe and effective cancer treatments for solid tumors.

References

  1. Bowles DW, O’Bryant CL, Camidge DR, Jimeno A. (2012) The intersection between cannabis and cancer in the United States. Critical Reviews in Oncology/Hematology 83(1):1-10.
  2. Lynch ME, Campbell F. (2011) Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. British Journal of Clinical Pharmacology 72(5):735-744.
  3. Pisanti S, Malfitano AM, Grimaldi C, et al. (2009) Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Best Practice & Research. Clinical Endocrinology & Metabolism 23(1):117-131.
  4. Salazar M, Carracedo A, Salanueva IJ, et al. (2009) Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. The Journal of Clinical Investigation 119(5):1359-1372.
  5. Caffarel MM, Andradas C, Mira E, et al. (2010) Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Molecular Cancer 9:196.
  6. Qamri Z, Preet A, Nasser MW, et al. (2009) Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Molecular Cancer Therapeutics 8(11):3117-3129.
  7. Flygare J, Sander B. (2008) The endocannabinoid system in cancer-potential therapeutic target? Seminars in cancer biology 18(3):176-189.
  8. Guzman M, Duarte MJ, Blazquez C, et al. (2006) A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. British Journal of Cancer 95(2):197-203.

Is Cannabidiol (CBD) An Effective Treatment for Epilepsy?

Stories of the ability of Cannabis  to alleviate seizures have been around for about 150 years (1).  Early randomized, placebo-controlled clinical studies conducted between 1978-1990 involving 48 patients with epilepsy found that daily treatment with 200-300 mg of cannabidiol (CBD) for up to 4 months was safe and well tolerated (2). However the small number of patients and short trial duration were not sufficient to draw any conclusions about CBD’s efficacy (1, 2)

Over the past decade, there have been reports that cannabis extracts with high concentrations of CBD may be effective anticonvulsants for children suffering from severe forms of uncontrollable epilepsy known as Dravet Syndrome and Lennox-Gastaut Syndrome (1, 3).  At present there are 9 ongoing or completed US clinical trials that evaluated the effects of CBD on epilepsy, treatment-resistant epilepsy, Dravet Syndrome (DS) and Lennox Gastaut Syndrome (LGS)

A Table that lists the ongoing clinical trials that are evaluating CBD as a treatment for epilepsy, DS, LGS and treatment-resistant forms of epilepsy can be found here.

Industry leaders in this field include GW Pharma and a relatively new entrant called INSYS Therapeutics Inc.  Of interest, in 2014, GW pharma’s Epidiolex, a liquid formulation of highly purified Cannabis-derived CBD was granted Orphan Drug Designation by the US  Food and Drug Administration (FDA ) as a treatment for Dravet and Lennox-Gastaut syndromes and other pediatric epilepsy syndromes.

More recently, a Phase 3, double blind, placebo-controlled study conducted with 120 children and young adults with Dravet syndrome and drug resistant seizures revealed that treatment with CBD (20 mg per kilogram of body weight) per day reduced the median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (4).  Further, the percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with CBD and 27% with placebo (4). The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (4).

Finally, adverse events that occurred more frequently in the CBD group as compared with the placebo group included diarrhea, vomiting, fatigue, sleepiness and abnormal liver function test results (4).

Similar results were observed in a randomized, double-blind, placebo-controlled trial CBD clinical trial conducted with 156 patients with Lennox-Gastaut Syndrome (5).

The results from these studies suggest that highly purified preparations of CBD may be effective in controlling patients who suffer from DS, LGS and other treatment resistant forms of epilepsy.  However, additional studies must be conducted with CBD with the goal of reducing the high frequency of adverse events associated with long term CBD treatment.

References

  1. Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia 2014; 55:783-786.
  2. Gloss D, Vickrey B. Cannabinoids for epilepsy. The Cochrane Database of Systematic Reviews 2014; 3:1-23
  3. Cilio MR, Thiele EA, Devinsky O. The case for assessing cannabidiol in epilepsy. Epilepsia .2014: 55:787-790.
  4. Devinsky O, Marsh E, Friedman D, Thiele E, Laux L et al. Trial of cannabidiol for drug-resistant seizures in the Dravet Syndrome. N Engl J Med 2017; 376:2011-2020
  5. Thiele, EA, Mazurkewicz-Beldzinska M, Denbadis, S, Marsh et al. Cannabidiol (CBD) significantly reduces drop seizure frequency in Lennox-Gastaut Syndrome (LGS): Results of a multi-center, randomized double-blind placebo-controlled Trial (GWPCARE4) American Epilepsy Society Annual Meeting. 2016. ( 1423_AES_Poster_LGS_)