I have described the Minnesota Medical Cannabis Program in a previous post. It is a unique program because it does not provide smokable cannabis for medical purposes. All of the cannabis is in a form that is vaporized, edible, absorbed through the oral mucosa, or transcutaneously after application to the skin. It is produced by two companies and made into products of varying amounts of tetrahydrocannabinol (THC), cannabidiol (CBD) . In the original matrix from the first post there appeared to be a total of about 11 products based on the THC and CBD ratios. For the purpose of this report the cannabis products were classified base on ratios of cannabinoids and route of administration according to the following table:
The program came out with a report on the experience of patients with chronic intractable pain using the program this week. They produce frequent reports and this is the latest. Although it is not a scientific study of the associated issues of pain relief it is interesting because of a number of considerations not the least of which is what happens when a state starts to manage a CSA Schedule 1 drug on their own and come up with their own process for certification and use.
The report details the cohort of patients who were qualified on the basis of intractable pain according to the following definition: “pain whose cause cannot be removed and, according to generally accepted medical practice, the full range of pain management modalities appropriate for this patient has been used without adequate result or with intolerable side effects.” (p 4).
The report focused on the results and side effects of 2245 patients certified by various practitioners for intractable pain between August 1, 2016 and December 31, 2016. It contains basic demographics of the patients and practitioners as well as a breakdown of the possible origins of their chronic pain. All of these details are available in the original report and I encourage any interested reader to find the details there. I am interested in the type of medical cannabis being used and the outcomes.
These details are fairly interesting from a descriptive standpoint. For example, just using the product definitions there is a distribution of how the products are purchased. The following bar graph illustrates the distribution of purchased products by THC and CBD content:
The report gets into more specific details about the types of THC and CBD products in each category and the average ingestion of these products per day in milligrams (mg). I am reproducing the first of a 4 page table here that contains progressively fewer patients in each strata:
It is apparent that very high THC products that are inhaled or ingested predominate the product distribution. Although the largest single group of patients were averaging 81.5 mg/day THC and 0.6 mg/day CBD the range is significant from 4.4 to 553.8 mg/day THC and 12.2 to 1,439.2 mg/day CBD.
Patient and treatment providers were asked to rate their degree of benefit from the medical cannabis program on a Likert scale where 1 = no benefit and 7 - great deal of benefit. Using that system 61% of the patients rated their experience as a 6 or 7 compared with 43% of the healthcare professionals rating the patient benefit as a 6 or 7. Specific benefits were rated and the top three included pain relief (56%), sleep improvement (10%), and reduction in pain medications and side effects (7%).
An area of interest in the report is whether or not the patient is reducing the amounts of other pain medications used in response to the use of medical cannabis. This question is asked to the certifying health care professionals. For this report, 586 responses of a total of 692 were used to determine that pain medications were reduced in 58% of the cases and not reduced in 48% of the cases. 221 reduced an opioid with 127/221 reducing the opioid by 50% or more. In addition, 16 reduced a benzodiazepine and 128 reduced a pain medication "other than an opioid or benzodiazepine" - but benzodiazepines are not pain medications. The full list of medications reduced or discontinued are available in Appendix E. Minnesota does have a Prescription Monitoring Program for controlled substances making it possible to quantify and confirm all of this data rather than depending on survey results.
The section of the report that I found most interesting was the section on a standard group of 8 symptoms followed in this patient group for improvement or no improvement. These symptoms are listed in the tables below.
It is an interesting report in that it gives improvements in symptoms over 4 months as well as the percentage of patients a 30% improvement in symptoms at some point in the initial 4 months, the percentage of patients who had a 30% symptoms improvement in the 4 month follow-up period, and the percentage of patients who had the 30% symptoms improvement and maintained it for at least 4 months. Only 11% of the pain patients maintained a 30% improvement in pain symptoms over the 4 month follow up despite higher ratings of initial pain relief. The most significant improvements were in nausea and vomiting.
Side effects were reported in the final section with about 10% of patient reporting severe side effects. These side effects included somnolence, sedation, headaches, dizziness, lightheadedness, confusion, fatigue, abdominal pain, mental fogginess, inability to concentrate, anxiety, panic attacks, and insomnia. Physical side effects were reported roughly twice as often as mental side effects and most were in the mild to moderate range. A typical metric found in clinical trials - medication discontinuation because of side effects was apparently not determined. In a series of statements included in the report, one patient stopped because of a lack of efficacy and there was a suggestion that stopping could occur for that reason or financial reasons but the data was not clear.
Although the current report is focused on intractable pain a couple of things seems clear. First, these reports are not scientific. There are no comparison drugs or placebos. Medical cannabis is added in many cases to a combination of existing opioid pain medications and benzodiazepines. In a purely qualitative sense, they do show what products are preferred by customers and these products contain significant amounts of THC. Second, in the case of the 8 symptom rating pain relief from medical cannabis appears to be modest at best. A significant number of patients acknowledged severe side effects, but were these side effects of the same level of severity that might be seen in a clinical trial? In those patients who replaced opioids or to a lesser extent benzodiazepines - was that because the initial medications were ineffective for pain or because cannabis has superior effects on pain?
The most interesting part of the data to me is that fact that medical cannabis is highly promoted for chronic pain. That promotion was initially political - for the purpose of legalizing medical cannabis. Currently it takes the form of cannabis saving people from opioid overdoses and this report makes an attempt to record reduced amounts of opioids use due to the cannabis. The problem is that it is all survey data. There are no standardized doses of cannabis and no attempt to determine a placebo effect. Physicians used to reading clinical trials need to ask themselves: Is a patient interested in using medical cannabis in Minnesota capable of answering the questions in an unbiased manner? Will their interest/belief in medical cannabis influence survey results? And if that is true - what does it mean that medical cannabis ends up with such a poor result for pain relief over a period of 4 months? I have concerns about the survey results based on my interviews with thousands of cannabis smokers. Although I am seeing people with significant addiction problems, I don't see the side effect frequency of insomnia, anxiety, panic, and paranoia that I am used to hearing hearing about. And in this group, I can't help but wonder how many of them have significant addictions? I also don't see a discussion of the fact that many opioid users commonly switch to cannabis when the opioid supply runs low or they make an attempt to stop using. There are potentially several mechanisms occurring in this population in addition to pain relief and side effects.
Another issue indirectly addressed by this report is what happens when you do an end run around the FDA? I have certainly been a critic of the FDA and its regulatory processes, but in the end there is always a study available for public discussion. That study typically has much more information content about drug efficacy and tolerability than the current Minnesota study because of the scientific design. This report is the type of data that you get when that regulatory hurdle is ignored.
The direction and legacy of medical cannabis in Minnesota seems to be contingent on the status of recreational cannabis. The program has been criticized for being too expensive compared with smokable cannabis. If Minnesota legalizes recreational cannabis, that may be the preferred route by many of the people in this program. Questions about the efficacy of cannabis in intractable pain remain unanswered despite all of the details in this report.
George Dawson, MD, DFAPA
References:
1: Minnesota Department of Health Office of Medical Cannabis. Intractable Pain Patients in the Minnesota Medical Cannabis Program: Experience of Enrollees During the First Five Months. Report
2: Desrosiers NA, Ramaekers JG, Chauchard E, Gorelick DA, Huestis MA. Smoked cannabis' psychomotor and neurocognitive effects in occasional and frequent smokers. J Anal Toxicol. 2015 May;39(4):251-61. doi: 10.1093/jat/bkv012. Epub 2015 Mar 4. PubMed PMID: 25745105.
Graphics:
All tables excerpted from reference 1 as a public document with no copyright.
