In the January issue of APM News we reported, in Clearing the Smoke, how increasing use of medical marijuana (MM) presents C-L psychiatrists with opportunities and dilemmas in equal measure. In this issue we focus on the effective control of epilepsy using medical marijuana in an interview with Davin Quinn, MD, Associate Professor, Department of Psychiatry and Behavioral Sciences, University of New Mexico.
Could you briefly explain the medical effectiveness of cannabidiol (CBD) in reducing epileptic seizures?
The mechanisms of action of cannabinoids are complex and not yet well-characterized.1 Endocannabinoid receptors (CB) are expressed throughout the brain and immune system. In general, the CB1 receptor modulates neuronal excitability by opening K+ channels and blocking Ca2+ channels. CB2 receptors are involved in immune regulation. However, CBD possesses a low affinity for CB receptors, and thus its anti-epileptic properties likely depend on other mechanisms.2 Much work remains to be done to understand the effectiveness of CBD in epilepsy.
New Mexico appears to have removed criminal penalties for medical cannabis (MC) in 2007. Has the uptake been gradual since then; or more pronounced in recent times—perhaps as more studies have shown its effectiveness?
New Mexico established its medical cannabis program in 2007, allowing for lawful production and use according to state regulations and guidelines. Applications for MC cards are increasing exponentially. In the summer of 2016 there were approximately 25,000 certified MC patients in the state of New Mexico; as of December 2017, more than 46,000 citizens have been approved for a medical cannabis card.3
Are the MC laws in New Mexico any more “lenient” than in other states for any reason, or standard/similar?
While there is significant variability in state MC programs, the New Mexico MC program and its guidelines appear fairly typical in scope compared to most other states. There are 20 conditions in New Mexico that qualify a patient for MC, including severe chronic pain, cancer, HIV/AIDS, and epilepsy. A physician’s diagnosis of a qualifying condition is required, along with documentation substantiating this diagnosis, and yearly filing of an application attesting that the patient is maintained on, or improving on, MC.
In your practice do you find that epilepsy patients are already self-administering MM before your treatment program, through home cultivation or purchases at state-licensed dispensaries?
Most patients are aware of medical cannabis for control of epilepsy, and this topic is discussed on the Epilepsy Foundation’s website, epilepsy.com. However, this does not mean it is widespread. Data from the Centers for Disease Control and Prevention indicate there are more than 23,000 epilepsy patients in New Mexico.4 with less than 4% possessing a MC card. Most patients have lingering questions about the risks and benefits, and what their providers think about MC.
Out of the 46,000+ people registered as MM users in New Mexico do we know how many are using it for epilepsy?
Yes—as of December 31, 2017, 649 are listed as using it for epilepsy. In comparison, over 22,000 are using it for posttraumatic stress disorder, and over 15,000 are using it for severe chronic pain.
Could you give one or two brief case studies from your personal experience showing the effectiveness of MM?
One patient with medically intractable epilepsy from a traumatic brain injury was on four anti-epileptics, with a vagal nerve stimulator implanted. He was experiencing five seizures daily with significant postictal agitation and mood dysregulation, often putting himself or his family at risk of physical harm. After starting medical cannabis, his seizure frequency decreased to one-to-two seizures daily, his agitation levels decreased significantly, and he became much easier for his family to manage at home.
Another patient with medically intractable epilepsy, treated with a left temporal lobectomy, was having frequent partial seizures with auras consisting of severe anxiety. After failing multiple anticonvulsants, he started medical cannabis, and found that his anxious auras decreased significantly.
With MC in epilepsy I have observed that a reduction in seizure frequency or intensity may be accompanied by an improvement in behavioral and emotional sequelae, such as reduced agitation and anxiety.
I’ve seen CBD described by regulators as a “safe and therapeutic treatment” for reducing/eliminating seizures—have you encountered any negative effects/risks? Are you worried about any risk of addiction leading to opioid disorder (against the current background arising from pain relief prescription)?
Negative effects and risks with CBD can be significant, and C-L psychiatrists should be aware of them.5 Side-effects such as fatigue, drowsiness, appetite change, vomiting, and diarrhea are common. There is a risk of intoxication with MC, especially if edibles are consumed in large quantities or in rapid succession, leading to disorientation, slurred speech, ataxia, or disinhibition.
If there is a significant concentration of tetrahydrocannabinol (THC) in the MC, then there may be increased risk of psychosis, paranoia, anxiety, and seizures. Cognition can become impaired on MC. There are potentially dangerous drug-drug interactions between MC and anticonvulsants such as with valproic acid and clobazam, that must be monitored. The risks associated with CBD appear comparable to those of conventional anticonvulsant medications.
On the one hand, the risk of increased rates of substance use disorders in patients starting medical cannabis must be considered and monitored. There is also the possibility that MC may reduce substance use. I observed one patient with traumatic brain injury, posttraumatic epilepsy, and significant inhalant use disorder who ceased using inhalants after starting MC.
You quoted (at the annual meeting preconference course) “up to 50% effectiveness shown in some research trials; in other trials, no significant difference.” I’ve seen March 2017 Australian research claiming a 90% reduction in seizures in adults with epilepsy (70% in children). Why the disparity?
Part of the discrepancy may come about from the reporting of absolute differences versus relative differences in studies. Another reason is the variability seen in randomized controlled trials of cannabinoids in terms of a) the patient population (adults vs children); b) the type of epilepsy treated; c) the type of cannabinoid compound studied; and d) the dose of the cannabinoid. These variables make side-by-side comparison of effectiveness rates difficult.
Are C-L practitioners designated “primary caregivers” under MM laws during treatment? Is the designation transferred to, say, a family member posttreatment? Are C-L practitioners at the forefront of MM use in New Mexico (or more widely), or is it in the portfolio of physicians generally? Is MM becoming a first-level treatment (rather than a follow-up after other interventions fail)?
According to the New Mexico Department of Health MC application, MC in New Mexico is meant to be a treatment to be used when a condition is “chronic and debilitating.” The decision of when to undergo a trial of MC is left to the provider (“primary caregiver”) and the patient, after the provider has explained the relevant risks and benefits and determined that the benefits outweigh risks. At this time, there is still a paucity of evidence demonstrating the associated risks and benefits of using MC for epilepsy. It is important that C-L providers who are asked about MC, or are considering certifying patients for MC for epilepsy, proceed forward in collaboration with neurologists and epilepsy teams, as well as in accordance with institutional, state, and federal regulations.
Do you foresee more states adopting MM laws, and federal law changing to bring about standardisation of practice? What issues/practices, if any, need to be standardised?
I anticipate there will continue to be wide variation in regulation and clinical use of MC from year to year, state to state, and institution to institution. There is a great need for further study of the different types of cannabinoids, their potential for benefit in epilepsy and other conditions, and their potential risks and side-effects.
1. Brodie MJ, Ben-Menachem E. Cannabinoids for epilepsy: what do we know and where do we go? Epilepsia 2017 Dec 6 [Epub ahead of print].
2. Rosenberg EC, Patra PH, Whalley BJ. Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. Epilepsy Behav 2017; 70:319-327.
3. New Mexico Department of Health. 2017 April 21. Medical Cannabis Program.
4. Zack MM, Kobau R. National and state estimates of the numbers of adults and children with active epilepsy—United States, 2015. MMWR Morb Mortal Wkly Rep 2017; 66:821–825.
5. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl JMed 2017; 376:2011-2020.