How recent advances in toxicology will revolutionize the medical cannabis industry: Part 3

There are two major revolutions unfolding whose paths are about to cross … not only for the betterment of the cannabis and hemp industries but for the future of toxicology as well.


Part 3: The Status of Medicinal Cannabis

Medicinal cannabis programs have now been established in the vast majority of states (38 so far), starting in 1996 with Prop 215/Compassionate Use Act in California -- where, curiously enough, this 20-year old program only recently overhauled its regulatory programs to ensure a greater degree of transparency and increase accountability (The Governor signed off on the changes just last week).  According to NORML, the following states have yet to adopt any sort of medicinal cannabis program: Idaho, Texas, Kansas, Nebraska, North and South Dakota, Louisiana, West Virginia, Arkansas, Indiana, Ohio and Pennsylvania.  Although it should be noted that these states are not closed to the issue and, in fact, all of them (with the exception of Idaho and Louisiana) have either approved or are considering legislation to establish industrial hemp programs (from which medicinal products can be derived like "hemp oil").  

Of course, every state program is different per its individual legislative mandates and operating conditions.  There are now many states that have separately approved the use of cannabidiol (CBD) oils for medical treatments: Utah, Wyoming, Oklahoma, Iowa, Missouri, Wisconsin, Kentucky, Virginia, Tennesee, North and South Carolina,, Mississippi, Alabama, Georgia and Florida.  It should be noted that other seemingly unconnected laws also impact the individual nature of each state's program ... such as banking and finance laws, product liability laws, and pre-emption/local control laws (not to mention how seemingly common terms like "institution of higher learning" may be defined differently by different state legislative code).  It is therefore, incredibly important, to deeply dive into your state's operating conditions (defined by both legislative mandates, state agency policies, and market and consumer needs) prior to joining the industry.

Medicinal cannabis (in all its forms) has a variety of different therapeutic uses, some with solid evidence bases and some without.  However, every state has a different list of "treatable conditions," which include several ailments for which there is not a solid evidence base. The largest medical dispensary in the world, Harborside Health Center in northern California, offers a web page listing the known treatable illnesses and popular information service Leafly lists a state-by-state compendium of qualifying conditions.  Some states only low-THC, CBD-enriched products to treat a narrow window of disorders or conditions, while other states have fairly monstrous lists.  Not to pick on Illinois, but it has the most sprawling list of treatable conditions and it would be hard to find solid evidence to support all these conditions (yet):

Qualifying conditions to become a medical marijuana patient in Illinois include:

  • Acquired Immunodeficiency Syndrome (AIDS)
  • Alzheimer's disease
  • Autism
  • Lou Gehrig's disease (ALS)
  • Arnold-Chiari malformation and syringomyelia
  • Cachexia/wasting syndrome
  • Cancer
  • Causalgia
  • Chronic inflammatory demyelinating polyneuropathy
  • Chronic post-operative pain
  • Chronic pain due to trauma
  • Chronic Pain Syndrome
  • Crohn's disease
  • CRPS (Complex Regional Pain Syndrome Type I)
  • CRPS (Complex Regional Pain Syndrome Type II)
  • Dystonia
  • Fibromyalgia (severe)
  • Fibrous dysplasia
  • Glaucoma
  • Hepatitis C
  • Human Immunodeficiency Virus (HIV)
  • Hydrocephalus
  • Interstitial cystitis
  • Intractable pain
  • Irritable bowel syndrome
  • Lupus
  • Multiple sclerosis
  • Muscular dystrophy
  • Myasthenia gravis
  • Myoclonus
  • Nail-patella syndrome
  • Neurofibromatosis
  • Osteoarthritis
  • Parkinson's disease
  • Post-concussion syndrome
  • Post-traumatic stress disorder (PTSD)
  • Residual limb pain
  • Rheumatoid arthritis (RA)
  • Seizures
  • Sjogren's syndrome
  • Spinal cord disease (including but not limited to arachnoiditis, Tarlov cysts, hydromyelia & syringomelia)
  • Spinal cord injury
  • Spinocerebellar ataxia (SCA)
  • Tourette syndrome
  • Traumatic brain injury (TBI)

The evidence base for therapeutic use of cannabis was reviewed most recently by Kevin Hill in JAMA, who reviewed the literature from 1948-2015 and focused on 28 randomized clinical trials using cannabinoids for conditions other than those approved by FDA (see below for info on FDA-approved cannabis products). He found that high-quality evidence supports the use of cannabis for chronic pain, nerve pain (neuropathy), and muscle spasms/spasticity due to MS or paraplegia.  In fact, the greatest interest might be the potential for cannabinoid pain medications to replace or complement opioid-based pain medications as the cannabinoids have been suggested to have an improved “therapeutic window” relative to opioids for pain control (Hayes and Brown 2014; JAMA Intern Med).  There's little question that cannabinoid therapy for chronic pain control poses a much lower potential for abuse than opioid-based therapies and absolutely no question that cannabis poses much lower acute toxicity! According to a June 2015 report by the Pew Charitable Trust, about 50% of deaths due to drug overdose (22,000 per year) are related to prescription drugs, including legally prescribed opioid narcotics.

The differences in treatable conditions across the states in relation to the amount of evidence supporting each type of therapy can lead to some challenging risk communication between doctor and patient.  In addition, patients get knowledge on the topic from social media sites and other poor-quality information sources.  For example, a recent meme on Facebook promised medicinal cannabis provided "34 cures for cancer," which appears to have been supported from an article listing 34 studies "proving cannabis cures cancer."  This is not to say there have not been some interesting discoveries in the world of cancer research; however, we are a long way off from being able to efficaciously treat tumors with cannabinoid therapy.  It must be noted that the collective ability of the scientific community to develop an evidence base is restricted by the current Schedule 1 status as dictated by the Controlled Substance Act of 1970 (although there is a measure currently in the Senate to change the classification of cannabis to Schedule 2, which would allow FDA, NIH etc. to fund larger research efforts).

One application of great interest is the use of CBD oils to treat epilepsy in children; however, the promise of these applications found on social media, etc. have so far outpaced the medical community’s ability to provide a solid evidence base.  CBD oils hold much promise for the treatment of "intractable" (severe) forms of epilepsy, such as Dravet and Lennox-Gastaut syndromes. However, like other forms of medicinal cannabis, detailed knowledge of toxicological mechanism and efficacy is still developing ... there are ongoing clinical trials for CBD oils in the treatment of severe epilepsy and many tech/pharma companies are out there competing in the marketplace.  

What we lack though is knowledge on the mechanism of toxicity as well as a completed mode of action framework (such as an Adverse Outcome Pathways, which I have described elsewhere) that shows the trigger points for bioactivity from the molecular level all the way up to the individual human level. A September 2015 publication in the New England Journal of Medicine reviewed the evidence for treatment of epilepsy, which I have described elsewhere. The conclusions of Friedman and Devinsky (2015) are that preclinical animal and in vitro data as well as some preliminary human data “may be effective in treatment with some patients with epilepsy” but “current data from studies in humans are extremely limited and no conclusions can be drawn.”

There are several FDA-approved medicinal cannabis products on the market today that should be mentioned.  The synthetic cannabinoid drugs dronabinol (Marinol® from AbbVie)  and nabilone (Cesamet® from Meda Pharmaceuticals) are used to treat nausea and vomiting due to chemotherapy; former also used to treat loss of appetite and “wasting” in AIDS/cancer patients. As of 2013, FDA was in clinical trial phase 3 with nabiximols (Sativex ® from GW Pharmaceuticals), a vaporized inhalant alternative to oral treatments currently available to treat chronic pain from cancer treatment (See Bostwick et al 2013; NEJM) which has now been approved in 27 other countries for treatment of spasms. In addition, the American Academy of Neurology published evidence-based guidelines in 2014 for the treatment of selected neurological disorders (including spasticity).

Currently, there are 273 clinical trials (of all type: ongoing, planned, withdrawn or complete) ongoing in US alone for the use of Sativex for a number of disorders. California, New York, Maryland and Massachusetts are associated with almost 60% of all US Sativex clinical trials.  One particularly noteworthy study to examine "behavioral pharmacology and toxicology of oral cannabis" is currently recruiting patients at my alma mater, Johns Hopkins University. 

Data and presentation from

Data and presentation from

It is important to note that these data are imprecise and the reader is encouraged to search at for more detailed information. For example, the aforementioned Johns Hopkins study will provide crucial human kinetics data that can help establish an adverse outcome pathway to allow for precise identification of biomarkers for clinical, workplace, regulatory and law enforcement needs. 

But I will discuss this concept and more in Part 4: Two Roads Converged in the Woods ...