Medications that utilize similar metabolic pathways (P450) and their importance in Cannabis ingestion (possible interactions):
As Cannabis nurses give care and educate those who engage in cannabis use along with polypharmacy, it is vitally important we have a general understanding of medication absorption and elimination, specifically the Cytochrome P450 (Cyp450) Pathway in order to recognize possible risks, benefits and medication interactions. For an in-depth look at the Cyp450 specifics, please refer to Project CBD's Primer on Cannabinoid-drug interactions By Adrian Devitt-Lee. https://www.projectcbd.org/how-to/cbd-drug-interactions
By assessing a patient's medication regimen and knowing what popularly prescribed drugs utilize common metabolic pathways, Nurses can better care for the patient inquiring about concurrent cannabis use.
According to Davis's drug guide for Nurses, "Drugs are primarily eliminated from the body by hepatic...or by renal elimination...therefore determining dosage regimens for patients with renal or hepatic impairment is important" (Deglin, et.al. 2015). "Drugs with CYP activity may be inhibitors, inducers or substrates for a specific CYP enzymatic pathway, thus altering the metabolism of concurrently administered agents" (McDonnell and Dang, 2013). A substrate is a drug or substance metabolized by the CYP450 enzyme. An inducing medication speeds up metabolism of medications, thus needing more of the medication. An inhibiting medication slows down metabolism of medication thus not needing as much and possibly experiencing adverse side effects. An example of an inhibiting medication interaction is that of grapefruit juice. Grapefruit juice has known to cause interactions when taken with medications such as statins, anti-arrhythmic medications, immunosuppressive agents, and calcium channel blockers (Deglin, et al 2015). Enzyme inhibition is dose dependent, so, the more grapefruit juice a patient drinks, the slower the medication is metabolized, risking possible adverse effects (Deglin, et al 2015). Current drug interactions with Warfarin/Coumadin and cannabis have occurred. A case study from the University of Alabama-Birmingham is available in the Project CBD primer.
For a patient wanting to add cannabis to their medication regimen, it is important we, as Nurses, understand the metabolism of cannabis in the body. According to Radical Health training, "THC is primarily metabolized by CYP2C9...there are more than 50 polymorphisms of this primary metabolic enzyme...CYP3A4 is responsible for most medication metabolism as well as THC/CBD elimination." It is important to note there are polymorphisms of this enzyme that alter cannabis metabolism. For example CYP2C9*3 and CYP3A4*22 have decreased enzyme activity resulting in cannabis sensitivity resulting in longer duration of action and stronger effects. While it is difficult to know if a patient has the predisposition for these polymorphisms, unless genetic testing has been done, thorough assessment of medications taken and symptom tracking is a way to detect and monitor for unpleasant interactions. Radicle Health also informs us that if CBD is ingested half an hour before other medications, inhibition occurs. Thus, risking possible side effects of the medication taken. Alcohol has also been reported to increase effects and serum levels of cannabis, according to Radicle Health.
By no means is the above table an exhaustive list of medications that utilize the CYP450 3A4 and CYP450 2C9 pathways, . Further studies are warranted in multiple areas related to pharmacology and cannabis use. What is important to note is, based on medications prescribed, nurses need to understand the possibility for drug-drug and drug-cannabis interactions, care for properly and educate as necessary. "By doing so will help aid in cannabis therapeutics gaining acceptance from physicians and patients thus progressing clinical studies" (Devitt-Lee, 2018).
Deglin, J.H., Vallerand, A.H., & Sanoski, C.A. (2015). Davis's drug guide for Nurses(14th ed.).Philadelphia,PA: FA Davis.
Indiana School of Medicine Clinical Pharmacology (2019) Cytochrome P450 Drug Interaction table. Https://drug-interactions.medicine.iu.edu/MainTable.aspx
McDonnell, A.M., & Dang, C.H. (2013, July). Basic review of the cytochrome p450 system. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093435/.
Table 3 from Opioid therapies and cytochrome p450 interactions. Semantic Scholar (1970, January 1). https://www.semanticscholar.org/paper/Opioid-therapies-and-cytochrome-p450-interactions./4db44bd9f95bce3fc791f518ada4527b94920462/figure/3.
Theisen, E., & Byars, T. (2019). Radicle Health Medical Cannabis Curriculum for Nurses.