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.

Regulatory Guidelines for Product Quality Are Necessary for the Success of the Medical Cannabis Industry

While medical cannabis products do not require federal regulatory approval by the US Food and Drug Administration (FDA) in states where it is legal, the emerging medical cannabis industry ought to adopt its regulatory guidelines and practices that assure the quality of all marketed US drugs and devices. This is because, at present, no universal regulatory guidelines or requirements exist to ensure medical cannabis quality and safety. Not surprisingly, the quality attributes of medical cannabis vary wildly from state to state and even between different locations within the same city, county or state. Clearly, this is not in the best interests of medical cannabis users.

FDA established mandatory federal quality guidelines to guarantee product safety, identity, strength and purity. According to FDA, product safety means that a product is free of unexpected side effects when it is used properly by a patient. Identity guarantees that a product is exactly what its label and related informational materials say it is. Strength means that a given product consistently delivers the correct dosage and potency over its shelf life from its manufacture to its expiration. Purity indicates that a product is free from physical, biological and chemical contamination.  Put simply, these guidelines guarantee consumers that products are safe, effective and meet defined quality attributes.

The agency has developed different sets of regulatory guidelines that ensure product quality during various phases of development, manufacturing and commercialization. The existing guidelines that are relevant to the medical cannabis industry include 1) Current Good Laboratory Practices (CGMP), Current Good Clinical Practices (CGCP) and Current Good Manufacturing Practices (CGMP).

CGLPs are the guidelines that regulatory laboratory activities during preclinical development of products. This includes data collection and documentation, creation of standard operating procedures (SOPs), safety and pharmacology testing in laboratory animals, and sample preparation, handling and storage. Traditionally, CGLP helps guide development and ensure the quality of individual molecules but can be applied to extracts, tinctures and other products derived from cannabis plants.

CGCP was developed to guide the planning, conduct and analysis of human clinical trials that are required before a prescription drug can garner FDA regulatory approval. While CGCP is not relevant for most medical cannabis growers and dispensaries, it is required for companies that are currently trying to develop cannabis-derived pharmaceuticals and related products.

The set of regulatory guidelines that is most appropriate for a majority of medical cannabis growers, formulators and dispensaries is CGMP.  CGMPs were developed to assure that:

  • Raw materials used in the manufacture of pharmaceutical and biotechnology products are of known and possibly standardized quality and are free from contamination
  • A manufacturing process is proven to produce a product that consistently meets its specifications and quality attributes
  • Adequate quality control and assurance testing measures have been employed to assure that a product meets its quality specifications at the time of release to market and at the end of its shelf life

There are 10 basic CGMP principles that help t o ensure product quality, safety and efficacy. They are:

  1. Proper design and construction of facilities
  2. Validation of facilities, equipment and manufacturing processes (materials testing, cleaning, software etc)
  3. Proper maintenance of equipment, facilities and utilities
  4. Creation of SOPs (and adherence to them)
  5. Documentation of all processes, data collection, record keeping etc
  6. Employee development, on-going training and certification
  7. Contamination protection and prevention
  8. Employee health and hygiene
  9. Product manufacturing records and reports (that enable product recalls)
  10. Audits and Inspections

Following these principles will help to create a process that produces a product that is reproducibly consistent, safe and effective.

Because FDA approval is not required for medical cannabis use in states where it is legal, there is no requirement that any CGLP, CGCP or CGMP must be implemented. That said, assuring product consistency, quality, safety and effectiveness will go a long way to help establish medical cannabis brand reputation and reliability.

References

  1. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=58  
  2. https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm090259.htm
  3. https://www.gpo.gov/fdsys/granule/CFR-2011-title21-vol4/CFR-2011-title21-vol4-part210

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

O Canada!

Unlike the patchwork of state-to-state regulations in the US, the Canadian government has published a single set of exhaustive federal guidelines that guide the licensing, growth, distribution and sale of medical cannabis throughout Canada. Not surprisingly, these extensive regulations have forced cannabis growers, dispensaries and other cannabis-related businesses to hire more employees to run their businesses.

According to a Calgary, Alberta-based staffing firm Cannabis at Work, the number of new legal Canadian cannabis jobs that will be created over the next couple of years is expected to be around 150,000. Giving a boost to this job growth is soaring demand for cannabis, which could reach 330,693 pounds in Canada next year.

And the types of jobs that will be in demand are not much different than the jobs that are in demand in other more established industries. For example, the current most in-demand jobs (with annual salaries) in the Canadian cannabis industry include

  • Marketing manager (CA$110,000)
  • Senior accountant (CA$98,340)
  • Quality assurance personnel (CA$90,750)
  • Human resources manager (CA$87,057
  • Cultivation manager (CA$87,050)

Other in-demand jobs are cultivation technicians, processing assistants, administrative assistant and sales personnel. Not surprisingly, explosive growth of the cannabis industry over the past two years has put enormous pressure on mature Canadian industries to stop their employees from jumping ship to cannabis startups that promise higher salaries, more generous benefit packages and less formal work environments.

Given the current political climate in the US (and a growing scarcity of white collar US jobs) migrating to Canada may not be such a bad idea for recent college graduates or life sciences professionals who are currently unemployed.  More important, for those of you who may be considering a move north the current exchange rate for the Canadian dollar is $0.75. So multiply the salaries listed above by 75% before taking the plunge. That said, the cost of living in Canada is less than that in the US and, of course, there is also socialized healthcare!

References

  1. http://cannabisatwork.com/ Accessed October 2, 2017