It’s very disquieting that delta-9-tetrahydrocannabinol (THC) is still considered a schedule I drug, labeled as devoid of medicinal merit and highly addictive. It’s nothing more than a catastrophic lie. As laws have relaxed, however, researchers are more frequently conducting studies that demonstrate the utility of cannabinoids for a startlingly wide range of medical conditions, including those qualifying conditions that enable prospective patients to obtain medical cannabis cards. There are other conditions that cannabinoids may be good for, however, and it’s no stretch of the imagination to say that cannabinoids are likely to be heavily involved in the future of medicine and overall wellness, especially considering what we know about the endocannabinoid system.
To that end, I recently spoke with Jahan Marcu, Ph.D., co-founder of the consulting firm Marcu & Arora, to hear his thoughts on the future of cannabinoid medicine. Marcu is also a recent addition to the Rolling Stone Culture Council, a position that Marcu seeks to use to “expand people’s awareness around some of the classic trips in the psychedelics space”, having recognized several psychedelics marketing gimmicks akin to those involving delta-8-THC and cannabidiol (CBD) marketing.
Jason S. Lupoi, Ph.D.: Your paper in 2010 demonstrated synergy between CBD and THC for treating aggressive brain and spinal cord cancer, so you saw 12 years ago that these molecules have medicinal merit. [1] How do you see cannabinoids playing out as a treatment option for cancer? Do you think that cannabinoids as a sole treatment option for cancer are a future possibility?
Jahan Marcu, Ph.D.: That is a really important question. When it comes to something like cancer or any health condition, there are many challenges and that’s where it’s best to take all available precautions and pursue all options. I rarely try to think of anything in life as a silver bullet for something. When I think about this question, I can speak for myself. I would explore every treatment opinion including dietary and lifestyle changes, chemotherapy agents, cannabis, etc. Anything as a sole treatment isn’t as effective as when coupled to a holistic approach. We should really move away from that idea of a sole treatment for anything.
What made our publication unique is that we proposed a molecular mechanism that is triggered when you add THC and CBD together. Therefore, between these two compounds, there’s reproducibility. The study helped in building on our knowledge of how to wield cannabinoids. I’m not sure how it works across the board with other cannabinoids. It depends on the cancer – in some cases, different cannabinoid preparations could be more useful. In some patients, perhaps THC causes adverse events; in others, maybe CBD does because the person has liver issues.
I’d still say THC and CBD, to me, have the most striking data regarding anticancer applications. Cannabinoid quinones have also shown remarkable anticancer potential. In the end, both singular and whole plant have their merits. We’re still at the point of trial and error.
JSL: As a scientist who has contributed to the cannabinoid medicine field, what are your comments regarding the fact that cannabis is still a Schedule I controlled substance at the federal level?
JM: I’m not at all surprised because the federal government has only created a mechanism for adding drugs, not removing them. There isn’t a clear process for this unless it is an FDA-approved formulated, packaged, and labeled product. Considering cannabis scheduling and the Drug Enforcement Agency has taught me that people don’t really understand the scheduling or the agency. It’s not a bunch of sheriffs; rather, It’s largely legal experts and lawyers.
We live in interesting times because THC appears in three scheduling categories. Marinol is schedule III, SYNDROS is schedule II, and plant-derived THC is schedule I. What’s the rationale? There’s no good answer. We might see more complex cannabis products getting national approval in the future and we should expect significant changes to create clear pathways for products that contain cannabinoids. The FDA wants people to engage with them.
Moving cannabis to something like schedule II will not do much to make cannabis easier to study in clinical trials, and everything in a dispensary would remain federally illegal and non-FDA approved. Even people who do not support cannabis legalization, such as Bertha Madras and Kevin Sabet, say that moving the plant to schedule II for the purposes of expanding research would be disingenuous. Maybe this move would help alleviate mandatory minimum sentences and sentencing disparities. Keeping cannabis under the control of schedule I has done a lot to impair public health issues. And what about semi-synthetic or artificially-derived schedule I drugs from hemp, such as delta-8-THC– what status are they? There has to be some change here, and I think it’s coming soon.
JSL: Legal, prescribed opioids have caused much harm to a sizable portion of society, causing some to become addicted to heroin or fentanyl. You have written about the effects of CBD during the management of opioid withdrawal. [2,3] What were the main findings of this research? Do you think that there’s merit amongst other cannabinoids, or the cannabis plant at large? What evidence have you seen that cannabis legalization has led to decreased harm from opioids?
JM: It’s really amazing – some of this research just came out and it’s great that people are getting access to the data! The drug abuse cycle is multifaceted. People can stop using a drug, relapse, have stress from not using the drug, lose their prescription, etc. There’re all sorts of factors. We’ve looked at different areas but it’s important to determine which stage. For example, are we talking about reducing opioid use or getting free of opioids? What stage of the opioid abuse cycle is being considered?
We observed over 80 patients who had been using prescription opioids during the first six months of becoming a medical cannabis patient in Delaware. [2] Our research found that there was at least a 30% decrease in opioid use! After that study concluded, I worked with another clinician who had a patient with a history of severe opioid abuse that was transitioning to naltrexone-based abstinence maintenance therapy following cessation of methadone. [3] The challenge of these types of pharmaceutical treatments is that, sometimes, you have to completely stop one drug treatment before you start another or the patient will experience precipitated, acute withdrawal. This experience can be detrimental to the treatment process. The patient informed the doctor that they were going to use a highly purified CBD product. So, there was a window where the person was going off of the opioid treatment, a transitionary phase to the abstinence of methadone, and CBD seemed to help this ONE person. That’s an important point, that this was just for one person, but it is incredibly promising research to me.
I do see value in cannabis at large too, because there is an association with having access to cannabis, and decreased opioid use.
JSL: At the 2018 Cannabis Learn conference in Philadelphia, I heard you speak on the “lethal dose” of THC and how much cannabis would need to be smoked over a given time duration to reach that level. Could you relate that LD50 into cannabis concentrates?
JM: The LD50 of THC has not been established in humans, but in lab animals, with pure THC, we find a range of values depending on the animal. It could be 100s to 1000s of mg/kg of body weight. The DEA website reports that 1000 mg/kg was the lowest dose that caused death in any animal. The estimated lethal dose of intravenously injected pure THC is 30 mg/kg, so for a 70 kg person (approx. 154 pounds), they would have to have 2,100 mg consumed intravenously.
With ingestion processes like dabbing, it’s not so much the compounds we know about that cause worry, but rather the byproducts of the extraction process. We’re lucky in a way because we have found that THC, CBD, CBN (cannabinol) have known risks. We don’t know the risks of the entourage of other cannabinoids. We may find that some cannabinoids are undesirable at any dose. Not every molecule within a plant is something that you will want to ramp up the concentration and ingest!
JSL: Of all the cannabinoids, which do you think hold the most promise for medicinal applications?
JM: THC, to me, still has vast, unlocked potential. The industry as a whole has not determined how to saddle it to take us where we want to go. We’re getting close. We’re throwing darts at a board and seeing where we get a hit. What we need to do is get strikes. A strike is a planned strategic move. We need to move away from the concept of getting hits and focus on getting strikes.
I’d also love to see CBG (cannabigerol) studied. There’s little to no safety data on CBG.
JSL: What medical conditions have you found cannabis to be especially adept at treating? Which conditions, in your opinion, that may not have been well investigated yet, does cannabis show promise for?
JM: We talk a lot about the top conditions: chronic pain, insomnia, and other difficult to treat diseases, but there are also orphan diseases that are rarer. It may not be worth creating an FDA-approved drug for an ultra-small demographic of people. Epidiolex™ received orphan drug status.
I think we should look into orphan conditions that affect a small number of people annually. Cannabis may be able to fill the role or make a great area of study. This approach may not make someone a lot of money, but cannabis may be worth looking at in those areas.
Another area that I am actively interested in is how cannabis affects psychedelics therapy. For psilocybin and other psychedelics therapy, what role does cannabis play? Could it be useful? I recently took a training to learn more about this. Perhaps there’s some phase of trauma therapy where cannabis may be useful or maybe you don’t want to use it. When you are considering any drug, it’s good to not just focus on the good side. If you understand where you can’t go with the drug, you can better understand where you can go. How’s that for some fortune cookie cannabis wisdom!
References
[1] Marcu JP, Christian RT, Lau D, et al. Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol Cancer Ther. 2010;9(1):180-189. [journal impact factor = 6.261; times cited = 115][2] Balu A, Mishra D, Marcu J, Balu G. Medical cannabis certification is associated with decreased opiate use in patients with chronic pain: A retrospective cohort study in Delaware. Cureus. 2021;13(12):e20240. [journal impact factor = N/A; times cited = 0]
[3] Shaw C, Marcu J. Case report: Cannabidiol in the management of acute opioid withdrawal. American Journal of Endocannabinoid Medicine. 2021;3(1):6-11. [journal impact factor = N/A; times cited = 14]
Good article