Novel Delivery Methods for Medical Cannabis Users

There is no doubt that vaping is better than smoking cannabis but even vaping can lead to respiratory problems. Moreover many medical cannabis users do not want the negative stigma commonly associated with “smoking weed.” Finally, in certain states, including New York, where medical cannabis is legal, dispensaries are not allowed to sell leaf or plant-like material to patients.  This is causing medical cannabis companies to figure out creative ways in which to deliver cannabinoid-based products and remain compliant with individual state mandates and cannabis regulations.

Interestingly, many of these so-called innovative delivery methods for cannabis are routine delivery technologies that have already been tested, refined and approved by the US Food and Drug Administration (FDA). or example,  Colorado-based Next Frontier Biosciences, founded by former biotechnology executives and research scientists,  recently created a micro dosing-based, nasal mist delivery system intended for the pain management market segment. Likewise, similar companies with biotechnology and healthcare backgrounds are also developing time-release transdermal patches, sublingual sprays and suppository-based systems.  These developments suggest that the medical cannabis industry is beginning to mature and is likely to become mainstream in the not-too-distant future.

A Little Dab Will Do You: Or Maybe Not?

Inhalable, noncombustible cannabis products are playing a leading role in the use of the medical and recreational cannabis products. Specifically, the practice of “dabbing” has exponentially grown in popularity in states where medical and recreational cannabis consumption has been legalized.

Dabbing involves inhaling vapors produced by placing a small amount of cannabis extract (a “dab”) on a small heated surface (the “nail”), which is connected to a water pipe ( 1 ). The most popular dabs are known as butane hash oil (BHO) dabs mainly because the concentrate is produced by passing the solvent butane over cannabis buds and leaves ( 2 ). Butane is subsequently removed from the extract under vacuum at room temperature or by heating in an oven. Differences in processing can lead to different dab consistencies that are colloquially known as shatter, budder, crumble, pull-and-snap, wax, etc (3, 4).

BHO have a tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations ranging between 50 and 90% (2). Consumers consider dabbing to be a form of vaporization, and, therefore, view it as easier on the lungs than smoking ( 5).

While delivery of harmfully-large amounts of cannabinoids (Pierre) may represent a potential danger to consumers, little is known about the toxicants that the process may produce. According to a recent paper entitled “Toxicant formation in dabbing: the terpene story (4) by a group of Portland State University researchers the high heat commonly used to heat dabs (concentrated cannabis extracts) exposes users to high levels of methacrolein (lung, throat and eye irritant), benzene (carcinogen) and other potential toxic degradation products which are known to pose human health risks (4).

The authors determined that the source of the potentially harmful degradation products may be the terpenes (compounds that give cannabis its odor and flavor) that are routinely concentrated in BHO dabs (4).  Myrcene is the most abundant terpene in cannabis, followed by limonene, linalool, pinene, caryophyllene, and humulene (4). Also, cannabis can contain trace amounts of up to 68 other terpenic compounds (6). Terpene content in BHO can range from 0.1 to 34% (4).

Another potential health risk is residual butane (a known carcinogen) that can be left behind if BHO dabs are not processed correctly (1, 2). Because of this, CO2 oil (another extraction method for dabbing) and alcohol extracts are the only allowable medical extracts to be sold under medical cannabis regulations in New York, Minnesota, Ohio and Pennsylvania (4). While commercially prepared BHO is on the rise in mature markets like California and Denver, much HBO is still made via “backyard-chemist” style operations so users beware.

Finally, while the results of this study are intriguing, I believe that much more research will be required to determine whether or not high heat terpene breakdown products pose actual health risks to dabbers.

References

  1. Stogner JM, Miller BL. The dabbing dilemma: A call for research on butane hash oil and other alternate forms of Cannabis. Subst. Abuse 2015; 36:393– 395
  2. Stogner JM, Miller BL. Assessing the dangers of “dabbing”: mere marijuana or harmful new trend? Pediatrics 2015: 136: 1– 3
  3. Pierre JM, Gandal M, Son M. Cannabis-induced psychosis associated with high potency “wax dabs” Schizophr. Res. 2016; 172:211– 212
  4. Meehan-Atrash J, Luo W, Strongin RM. Toxicant formation in dabbing: the terpene story ACS Omega, 2017; 2:6112–6117
  5. Gieringer D, St. Laurent J, Goodrich S. Cannabis vaporizer combines efficient delivery of THC with effective suppression of pyrolytic compounds J. Cannabis Ther. 2004; 4:7 – 27
  6. Ross SA, ElSohly MA. The volatile oil composition of fresh and air-dried buds of Cannabis sativa J. Nat. Prod. 1996: 59:49– 51

Cannabis Pharmacokinetics, Metabolism and Detection

THC (Δ-9-tetrahydrocannabinol) is the main psychoactive cannabinoid found in cannabis and the primary molecule used for detection among cannabis users. Therefore, it is important to understand THC’s pharmacokinetics (distribution in the body), its metabolism (how it is broken down by the body) and the basis of the laboratory tests used for its detection.

The primary routes of administration of cannabis include smoking/vaporization and ingestion. Not surprisingly, the route of administration affects the absorption characteristics of THC. When cannabis is smoked or vaporized, there is a rapid onset of action (within minutes) with absorption of roughly 10%-35% of available THC in the product (1). THC is mainly absorbed through the bloodstream (2).

Peak THC plasma concentrations (blood levels) occur within 8 minutes after smoking or vaporization (1). In contrast, onset of action following ingestion occurs within 1-3 hours with 5%-20% absorption of THC (1). Peak plasma levels are observed after 2-6 hours after ingestion (1).

THC is primarily metabolized via the liver cytochrome P450 (CYP) system into a psychoactive compound, 11-hydroxy-THC (11-OH-THC) (2). 11-OH-THC is further metabolized into several inactive forms with 11-nor-9-carboxy-▵ 9-tetrahydrocannabinol (THC-COOH) as the dominant inactive metabolite (2). Because THC is highly lipophilic (fat-loving) it is mainly distributed in adipose (fat) tissue, liver, lung and spleen (1, 2).

THC’s elimination half-life —50% elimination of the initial absorbed dose of THC—can range from 2-57 hours following inhalation. The half-life of 11-OH-THC (the active metabolite of THC) is 12-36 hours (1, 2). Twenty (20) percent of THC is excreted in the urine whereas up to 65% is eliminated in feces (2). Within 5 days, nearly 90% of THC is eliminated from the body (2).

Urine immunoassays are typically used to detect THC-COOH in persons being tested for cannabis consumption. After a single use, THC can be detected in the urine for up to 7 days. With chronic cannabis consumption, THC can be detected in urine for 10-30 days. A sensitive test called enzyme-multiplied immunoassay technique (EMIT) can detect urine levels as low as 20-100 ng/ml.

Results from these screening tests indicate prior cannabis exposure but they cannot determine the amount used or degree of clinical effects after use. At present, detection of 50 ng/mL is considered positive for employees undergoing drug testing.  False-positive results can occur with ibuprofen, naproxen, dronabinol, efavirenz, and hemp seed oil. False-positive test results are unlikely from second-hand smoke inhalation, unless this exposure occurs in an unventilated space (1).

Blood tests can also be used to detect THC; however, detected levels cannot be associated with clinical effects. Hair sampling tests that use gas chromatography and mass spectrometry assays are available for cannabis screening. These screening methods can be used to test for multiple cannabinoids, including THC, THC-OH, THC-COOH, CBN and CBD (3). Cannabinoids enter the hair through capillaries and sweat and can be detected up to 3 months after exposure (3, 4). However, detection depends on heaviness of use and potency of marijuana consumed (4). 

References

  1. Russo L, Caneva D Cannabinoid poisoning. http://emedicine.medscape.com/article/833828-overview#a5  Accessed Aug. 9, 2017
  2. Sharma P, Murthy P, Srinivas Bharath MM Chemistry metabolism and toxicology of cannabis: clinical implications Iran J. Psychiatry 2012; 7:149-156
  3. Huestis MA, Mitchell JM Cone EJ Detection times of marijuana metabolites in urine by immunoassay and GC-MS J Anal Toxicol 1995; 19:443-449.
  4. Taylor M, Henderson R, Lingford-Hughes A, Macleod J, Sullivan J, Hickman M Comparison of cannabinoids in hair with self-reported cannabis consumption in heavy, light and non-cannabis users. Drug Alcohol Rev. 2017; 36-220-226.

What is CBN And Why It May Be Important

Cannabinol or CBN is a weak psychoactive cannabinoid found only in trace amounts in Cannabis (1).  It is mostly a degradation product (metabolite) of Δ-9-tetrahydrocannabinol (THC) [2].

Studies suggest that CBN acts as a weak agonist of CB1 receptors and has a higher affinity for CB2 receptors albeit lower than the affinity of THC for CB2 receptors (3, 4)..

Because CBN is a partially-selective agonist of CB2 receptors it has been suggested to have a plethora of therapeutic benefits including 1) pain relief, 2) sedative effects, 3) anti-inflammatory and antibacterial activity, 4) anticonvulsive properties, 5) bone growth promotion and 6) appetite stimulation (5-9). However, it is important to note that much more research must performed with CBN to validate or refute its potential therapeutic and clinical effects.

References

  1. Karniol IG, Shirakawa I, Takahashi RN, Knobel E, Musty RE. (1975) Effects of delta9-tetrahydrocannabinol and cannabinol in man. Pharmacology 1975; 13:502-512.
  2. McCallum ND, Yagen B, Levy S, Mechoulam R. Cannabinol: a rapidly formed metabolite of delta-1- and delta-6-tetrahydrocannabinol. Experientia 1975; 31:520-521.
  3. Mahadevan A, Siegel C, Martin BR, Abood ME, Beletskaya I, Razdan RK. Novel cannabinol probes for CB1 and CB2 cannabinoid receptors. Journal of Medicinal Chemistry  2000; 43:3778-3785.
  4. Petitet F, Jeantaud B, Reibaud M, Imperato A, Dubroeucq MC. Complex pharmacology of natural cannabinoids: evidence for partial agonist activity of delta9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. Life Sciences 1998; 63:1-6.
  5. Zymont PM, Andersson DA, Hogestatt ED  Δ-9-tetrahydrocannabinol and cannbiol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism  J Neurosci 2002; 22:4720-4727.
  6. Appendino G, Gibbons S, Giana A, Pagani A et al. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study.  J Nat Prd 2008; 71:1427-1430.
  7. Ludovic Croxford J Yamamura T. Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? J.Neuroimmunol. 2005: 166:3-18.
  8. Farrimond JA, Whalley BJ, Williams CM Cannabinol and cannabidiol exert opposing effects on rat feeding patterns.  Psychopharmacology (Berl) 2012; 223:117-129.
  9. Cannabis 101: What is CBN and what are the benefits of this cannabinoid? https://www.leafly.com/news/cannabis-101/what-is-cbn-and-what-are-the-benefits-of-this-cannabinoid  2015. Accessed August 3, 2017

Development of a Molecular Test That Identifies Strains of Cannabis sativa

As the legal cannabis industry continues to mature, it has become increasingly apparent that the need for rapid and simple tests for forensic investigations and industrial quality control has become crucial.  To that end, a group of Japanese investigators developed a polymerase chain reaction (PCR) method called loop-mediated isothermal amplification (LAMP) that can differentiate Cannabis sativa from hemp (1, 2).

The assay is based on gene amplification of highly conserved DNA sequences of the tetrahydrocannabinolic acid (THCA) synthase gene that plays a major role in the Cannabis THC biosynthetic pathway.  Researchers used this test on 21 known Cannabis sativa varieties and were able to detect THCA sequence in each of them within 90 minutes (1).  In additional experiments, the researchers were able to distinguish between multiple strains of Cannabis sativa (which all possessed THCA DNA sequences) and multiple varieties of hemp (which do not possess detectable THCA sequences (2).  Based on these results, the researchers suggested that LAMP represents a rapid, sensitive, highly specific and convenient (in the field) method for detecting Cannabis sativa and differentiating it from non-psychoactive Cannabis varieties.

While this research represents a step in the right direction for forensic analysis and industrial Cannabis quality control, LAMP in its current form does not allow differentiation between different varieties of Cannabis sativa. Additional molecular analyses of different Cannabis genomes and a more in depth evolutionary analysis of genetic divergence in THCA genes from different cannabis varieties will be required to make this test useful in forensic analysis of different cannabis brands and industrial quality control programs.

  References 

  1. Kitamura M, Aragane M, Nakamura K, Watanabe K, Sasaki Y  Development of Loop-mediated isothermal amplification (LAMP) assay for rapid detection of Cannabis sativa Biol Pharm Bull. 2016; 39:1144-1149.
  2. Kitamura M, Aragane M, Nakamura K, Watanabe K, Sasaki Y  Rapid identification of drug-type strain in Cannabis sativa using loop-mediated isothermal amplification assay. J Nat.Med 2017;71:86-95.

A Cannabis Factoid

According to a 2016 article in Wired Magazine, in 1993, the average THC content in commercially available cannabis was roughly 3 percent by weight. By 2008, through traditional breeding programs, the THC content (potency) had nearly  tripled.  In 2017, analyses suggested that the world wide THC content of some strains of cannabis may be 12-16 percent or as high as 37 percent by weight (1-5). Recent genetic analysis suggest that this increase may be a  result of gene amplification with high THC-producing plants having multiple copies of THC biosynthetic genes.

Many cannabis  industry experts contend that the exponential increases in THC levels  can be directly attributed to the so-called “war on drugs” that forced illegal growers to abandon outdoor cultivation in favor of indoor growing operations. Unlike outdoor growing operations, indoor cultivation permits more controlled growing environments, less need for pesticides  and a reduced likelihood of theft of mature plants.  However, as the concentration of THC increased, so did prevailing market prices of cannabis. These price increases helped growers to absorb the higher cost  of indoor climate control and artificial lighting without cutting into profit margins. Ironically, however, the legal use of cannabis for medical and recreational use in many US States, has allowed growers to move their illicit indoor growing operations into legal, full scale greenhouse cultivation.  This, in turn, is currently causing the the price of cannabis to plunge in many states.

While THC concentration are at all time highs (pun intended), less attention has been paid to genetic manipulation of cannabis plants for medicinal use that contain high levels of cannabinoids other than THC. This area represents the next era of genetic manipulation of the Cannabis genome.

Stay tuned…..

References

  1. Radwan MM, Elsohly MA, Slade D, Radwan MM et al. Cannabinoid ester constituents from high-potency Cannabis sativa Phytochemistry 2008 69:2627-26-33
  2. Niesink RJ, Rigter S, Koeter NW, Brunt TM, Potency trends of delta=(9)-tetrahydrocannabinol, cannabidiol and cannbinol in cannabis in the Netherlands 2005-2015. Addiction 2015; Aug1 [Epub ahead of print]
  3. Swift W, Wong A, Li KM, Arnold JC, McGregor I Analysis of cannabis seizures in NSW Australia: cannabis potency and cannabinoid profile. PLoS one 2013; 8: e70052
  4. Zamengo L, Frison G, Bettin C, Sciarrone R, Variability of cannabis potency  in the Venice area (Italy): a survey over the period 2010-2012. Drug Test Anal 2014:6:46-51
  5. Bruci Z, Papoutsis I, Athanaselis S, Nikolaou P, et al. First systematic evaluation of the potency of Cannabis sativa plants grown in Albania Forensic Sci In 2012; 222:40-46.

 

 

 

Commercializing Cannabis-Derived Pharmaceuticals: Legal and Regulatory Challenges

The current regulatory and legal landscape for cannabis and cannabis-derived products is extremely difficult and fraught with numerous challenges. For example, in the US, cannabis and products derived from it (including hemp) are federally classified as Schedule I drugs according to the US Controlled Substances Act (1). This means that cannabis and its products have been deemed to have “no currently accepted medical use in treatment in the US” (heroin and LSD are also schedule I drugs), are harmful and consequently, are illegal (2).

Not surprisingly, its Schedule 1 classification has seriously hindered cannabis research in the US and made it extremely challenging for drug companies developing cannabis-derived pharmaceutical products (3). However, over the past decade or so, 29 states including the District of Columbia have enacted legislation that permits some form of cannabis consumption for medical purposes (4). Yet, despite this, cannabis and products derived from it remain illegal at the federal level and during interstate transport (even between states where medical marijuana has been legalized) is illegal and criminally punishable (2).

The confusion regarding cannabis use at the state and federal levels has given rise to two distinct types of companies that are attempting to commercialize cannabis (and products derived from it) for medicinal purposes. The first of these are commonly referred to as medical marijuana or medical cannabis companies. Typically, products from these companies are botanical extracts or actual plant materials derived from specific cannabis strains with anecdotally-reported medicinal properties that can be topically applied, ingested, smoked or vaporized. Patients require a “prescription” (card) from a state-licensed physician to obtain medical marijuana and it can only be used in states that permit consumption of cannabis for medical purposes. It is important to note, that while a prescription is required for medical cannabis use, these products do not require human clinical testing for safety, tolerability and efficacy (like other prescription drugs) prior to their sale in states where medical marijuana is legal.

In contrast with medical marijuana companies, biopharmaceutical companies including GW Pharma, Zynerba, Insys, Kannalife, Aphios and others (Table 1) are committed to developing cannabis-derived pharmaceuticals using conventional US Food and Drug Administration regulatory approval pathways. UK-based GW Pharma is the clear leader in cannabis-derived pharmaceutical space—its flagship product Sativex®, a plant extract, has been approved as a treatment for cancer-related pain and MS spasticity in 27 countries outside the US (5).

While the business case for developing pharmaceutical cannabis-derived pharmaceuticals is a sound one, the time and cost necessary for regulatory approval will be much greater than that for commercializing medical marijuana. At present, the United State Food and Drug Administration (FDA) has signaled a willingness to review new drug applications for cannabis-based pharmaceuticals (6). However, the agency has yet to issue definitive guidance for regulatory approval of these products and to date has not approved any application for cannabis-based products (6). Nevertheless, garnering FDA regulatory approval for cannabis–derived pharmaceuticals may offer several competitive advantages over numerous medical marijuana products that currently dominate the US market.

First, the average cost per patient of Sativex® to treat MS spasticity in countries where it has been approved has been estimated to be roughly $16,000 (6). Several studies indicate  (7, 8) that the high price of Sativex® will make it unlikely to be considered cost effective by regulators in countries with government-mandated national formularies like the UK, Ireland and Australia. However, this should not be an impediment in the US market because the federal government does not set drug prices and third-party payers dictate formulary placement and set drug reimbursement rates.

Second, unlike medical marijuana (which as previously state is a Schedule 1 drug), FDA approved cannabis-based pharmaceuticals like dronabinol and nabilone have been classified or reclassified as Schedule 2 (opioids) or Schedule 3 (codeine) drugs (5, 9). Federal regulators are likely to apply the same scheduling criteria to the next generation of FDA-approved cannabis-derived pharmaceuticals like Sativex® and others. Rescheduling will effectively allow these products to compete with medical marijuana because unlike medical marijuana—which is legal in only 29 states and cannot be transported across state borders—approved cannabis-derived pharmaceuticals can be legally prescribed, sold and used in all 50 states and US territories.

Finally, and perhaps most importantly, physicians may be inclined to prescribe FDA-approved cannabis drugs as compared with medical marijuana because they have been evaluated in human clinical trials and officially deemed to be safe and effective treatments for specific therapeutic indications.. In marked contrast, medical marijuana can be prescribed and sold in states where it is legal without going through any formal drug review process. While this is unlikely to interfere with possible therapeutic benefits offered by medical cannabis questions concerning product safety, effectiveness and reproducibility about these products are likely to continue to  arise until industry best practices are implemented and standardized.

References

  1. https://www.deadiversion.usdoj.gov/21cfr/21usc/812.htm  Accessed July 17, 2017
  2. https://www.dea.gov/druginfo/ds.shtml  Accessed July 17, 2017
  3. https://www.brookings.edu/wp-content/uploads/2016/06/Ending-the-US-governments-war-on-medical-marijuana-research.pdf  Accessed July 17, 2017
  4. http://medicalmarijuana.procon.org/view.resource.php?resourceID=000881 Accessed July 17, 2017
  5. https://www.gwpharm.com/products-pipeline/sativex  Accessed July 17, 2017
  6. https://www.fda.gov/newsevents/publichealthfocus/ucm421163.htm  Accessed July 17, 2017
  7. Pharmacoeconomic NCF. Cost-effectiveness of Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®) as add-on treatment, for symptom improvement in patients with moderate to severe spasticity due to MS who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy. 2014. http://www.ncpe.ie/wp-content/uploads/2013/01/Summary-v1.pdf.
  8. Lu L, Pearce H, Roome C, Shearer J, Lang IA, Stein K. Cost effectiveness of oromucosal cannabis-based medicine (Sativex(R)) for spasticity in multiple sclerosis. PharmacoEconomics. Dec 1 2012;30(12):1157-1171.
  9. https://www.deadiversion.usdoj.gov/fed_regs/rules/1998/fr1105.htm  Accessed July 17, 2017

Treating Cancer-Related Symptoms with Cannabis

In the 1970s, purified and synthetic cannabinoids were being evaluated as palliative treatments for cancer related symptoms (1). One of the earliest recognized clinical indications for cannabinoids was cancer induced nausea and vomiting (CINV) [2].

A 1988 prospective open label trial found that inhaled cannabis effectively controlled CINV in 78% of 56 cancer patients who had inadequate control of nausea and vomiting with conventional anti-emetics (3). Also, a later report that evaluated 30 trials and over 1300 participants determined that synthetic THC molecules such as nabilone and dronabinol were more effective than conventional anti-emetics in controlling acute CINV (2). This led to the early approval of dronabinol and nabilone as treatments for CINV but their use as a treatment for CINV has not been widespread (2,3)

A quick search of the clinical trials site www.clinical trials.gov revealed that there are no US clinical trials currently underway to further evaluate the use of Cannabis as a treatment for CINV.  Moreover, there are no natural Cannabis products e.g. extracts, sprays etc, on the market today that have received US Food and Drug Administration (FDA) approval as a treatment for CINV.

Inhaled Cannabis, and extracts containing THC and CBD have been clinically found to be more effective in treating cancer-related neuropathic pain than placebo (3, 4) but their effectiveness compared with conventional pain medications is uncertain (2). Yet, despite this, GW Pharma’s Sativex® (an extract that contains 1:1 ratio of Δ-9-tetrahydrocannabinol (THC) and cannabidiol [CBD]) is an approved treatment for cancer-related pain in 27 countries outside of the US (5).

There are currently 4 US clinical trials in (various phases) that are underway to determine the effects on Sativex® on advanced cancer pain and chemotherapy-induced neuropathic pain (Table 1). Regulatory experts expect Sativex® to garner FDA approval for both indications.

References

  1. Guzman M, Duarte MJ, Blazquez C, et al. A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. British Journal of Cancer 2006; 95:197-203.
  2. Tramer MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 2002; 323:16-21.
  3. Bowles DW, O’Bryant CL, Camidge DR, Jimeno A. The intersection between cannabis and cancer in the United States. Critical Reviews in Oncology/Hematology 2012; 83:1-10
  4. Notcutt W, Price M, Miller R, et al.  Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘N of 1’ studies. Anaesthesia 2004; 59:440-452.
  5. https://www.gwpharm.com/products-pipeline/sativex  Accessed July 12, 2017

 

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 Possesses Antibacterial Properties Against MRSA

There is a growing body of evidence that suggests that Cannabis can be used to treat a wide variety of symptoms associated with chronic illnesses and conditions.   That said, the findings of Giovanni et al in a paper entitled “Antibacterial Cannabinoids from Cannabis sativa: A Structure-Activity Study” (1) suggest that several cannabinoids may be useful to treat infections caused by antibiotic resistant bacteria including MRSA (methicillin-resistant Staphylococcus aureus).

The results from this study showed that five major cannabinoids including cannabidiol (CBD), cannabichromene (CBC),
cannabigerol (CBG), Δ9-tetrahydrocannabinol (THC), and cannabinol (CBN) showed potent antibacterial action against 6 clinically-relevant strains of MRSA. The minimum inhibitory concentrations (MIC) of these compounds ranged from 0.5 µg/ml to  2 µg/ml  (Table 1)

Table 1. MIC (µg/ml) of Cannabinoids Against Drug Resistant Strains of S. aureus (adapted from Reference 1)

Cannabinoid SA-1199B RN-4220 XU212 ATC5923 EMRSA-15 EMRSA-15
CBD 1 1 1 0.5 1 1
CBC 2 2 1 2 2 2
CBG 1 1 1 1 2 1
THC 2 1 1 1 2 0.5
CBN 1 1 1 1 1

While the mechanism of action of cannabinoids against MRSA remains unknown, the results of this study suggest that additional studies ought to be carried out to determine whether or not cannabinoids may be useful to combat infections caused by multidrug resistant strains of bacteria.

References

  1. Appendino A, Gibbons S, Giana A, Pagani A Grassi G,Stavri M,Smith E Rahman M. Antibacterial cannabinoids from Cannabis sativa: A structure-activity study J. Nat. Prod. 2008: 71:1427-1430