CBD Contraindications

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Some people appear to be allergic to Cannabis in different forms; some to the fresh leaves, others to the smoke, and for others the Cannabinoids or Terpenes. Here are known and potential contraindications for Cannabidiol (CBD), from Kevin McKernan of Medical Genomics:

“Most drugs are metabolized by the liver. P450 cytochromes are responsible for metabolism of a variety of Anti-Epileptic Drugs (AED). Some AEDs are potent inhibitors of these enzymes, and can exacerbate the side effects of another AED. Patients with variants in these p450 cytochrome genes can have altered cytochrome enzymatic activity resulting in complications with certain AEDs. Of particular note is that CBD appears to be a potent inhibitor of CYP3A isoforms which are involved in the metabolism of Clobazam to desmethyl Clobazam.

Most Dravet’s patients have missense mutations in the SCN1A gene (sodium channel). GW Pharma has published work demonstrating CBD’s lack of affinity for sodium channels. There is prolific literature on CBD impacting calcium regulation via PPARgamma.

Clinical trial reviews on CBD are fairly neutral to skeptical over the design of previous CBD trials. The toxicity is reported to be very low and well tolerated, but the double-blinding and placebo controls are often lacking.

There has also been a reported case of Sevoflurane contraindication with CBD. Patients using Sevoflurane-based anesthesia usually regain consciousness in 25 minutes after the gas is removed. In one case, a patient who was on CBD regained consciousness, unharmed, after approx. 6 hours. Sevoflurane is also often co-administrated with Nitric Oxide (NO) which is also in the PPARgamma pathway. The CBD dosage on the patient noted above was unknown, as this was self administered unbeknownst to the practicing physicians. This child was almost intubated, but fortunately a physician who was highly knowledgeable on CBD knew this was a mistake, and it was best to let time take its course.

Because CBD has a very low affinity for CNR1, the mode of interaction with Sevoflurane may be related to its uncontested and thoroughly reported calcium regulation in the mitochondria. CBD’s interactions with PPARgamma are well published, but the suggested contraindication with Sevoflurane is speculation at this point and needs more research. The one patient which experienced this adverse event had a de novo nonsense mutation in the D4 location (nucleic acid position 4693) of the SCN1A receptor. A nonsense mutation knocks out the rest of the C-terminus protein which contains the Calmodulin binding domain. Nonsense mediated decay was not reported, but CBD did limit the seizures.

Dravet Syndrome is not always limited to SCN1A mutations. 10-12% can be mutations in other genes.

Certain compounds found in some foods can influence cytochromes. Bergamottin in grapefruit juice can inhibit some cytochromes, leading to longer effective dosages of AEDs which are dependent on these same cytochromes. [Look for the “grapefruit warning” on your prescription medicines.]

“Adolescent Cannabis Use IQ” (Meier) is the most-frequently cited study in regards to IQ and Cannabis use. This has been presented as a risk to Dravet children, but scientists voicing these concerns may not be aware of all of the papers in this space to put this risk into proper perspective. The Meier paper demonstrates a slight decay in IQ for “cannabis use.” This is likely THC-rich recreational cannabis, but the paper does not address the source. This is a major flaw in reasoning, as it assumes all cannabis is the same. Sequence data from the genomes of cannabis and humans demonstrates cannabis plants are >10 fold more variable than humans. It is well known that compound levels (THC, CBD, etc.) in cannabis can vary dramatically. Likewise, other cannabinoids and terpenes are frequently not measured in such studies making it difficult to correlate this risk to epilepsy patients using predominately CBD-rich cannabis.

To put this into perspective, one might also consider the impact of AEDs, or even legal drugs like ethanol, on one’s IQ. A good functional MRI (fMRI) study on ethanol vs Cannabis demonstrates far more harm from ethanol exposure than cannabis. As for epilepsy patients, the risk that prolonged exposure to phenobarbitol (an approved AED) could alter and/or damage the development of a child’s brain is real, and should be put into perspective when thinking about the use of CBD (or even THC), which are relatively safe compounds.”

Click for Two Year Old Kids Can’t Read: 587 drugs (4160 brand and generic names) are known to interact with cannabis (THC & CBD)

Click for Medical Cannabis Adverse Effects & Drug Interactions (PDF)

Click for Known and potential side effects of Cannabidiol (CBD)

Click for CBD Use, Cautions, Contraindications

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