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CBD and the Entourage Effect: Excerpt from Dr. Kachmann's New Book (available on Amazon)

The Cytochrome P450 System (CYP)

CBD or THC, along with the rest of the cannabinoids they contain, will eventually have to be metabolized by the gut, liver, and occasionally other parts of the body. The cytochrome system, abbreviated CYP, is the most important system involved with cannabis metabolism. It accounts for 75% of the enzymes involved with medication metabolism in general.

There are 60 CYP genes; however, only a few are tested for when prescribing cannabis. What concerns me a great deal is that people are buying cannabis products like CBD without age restriction and have no idea that they have the chemical power to turn off the metabolizer of many of the medications they’re taking.

CYP enzymes are involved with catalyzing, upgrading, or downgrading a vast number of reactions, mostly in the liver. CYP can detoxify medicinal compounds to facilitate excretion, or turn inactive compounds into active pharmacological agents.

For example, if CYP enzymes metabolize a drug slowly, the drug stays longer in the body. If it metabolizes a drug more quickly, a higher dose may be needed to have an effect. Many medications in other substances, such as alcohol, can lead to synthesis of other CYP enzymes, making it more metabolically active.

You can see if someone is going to take CBD products, they would need to be going to a physician who is highly trained in the pharmacology of drug interactions. But that will not happen in today’s free-for-all of buying CBD products. I doubt there will be a medical provider at the gas station.

There are several CYP enzymes that can be tested for prior to use of cannabinoids. The first one is CYP2D6. This enzyme acts on 25% of all known drugs, including cannabinoids. As you already know, this would only occur in very rare situations. The law signed by the Indiana House, Senate, and Governor’s office did not include mandatory testing for people who are taking other medications. A wide variety of medications, as well as grapefruit juice and CBD products, work as strong inhibitors of the P450 enzyme, which may amplify or weaken their response to the drugs the patient is already taking. Sorry that I keep on repeating that, but it may help you avoid complications—or even death.

The extent to which CBD behaves as a competitive inhibitor of Cytochrome P450 depends on how and how much CBD is administered. Every person responds differently, and it can be a serious problem even when they are not on multiple other medications. This means that patients ingesting CBD products should pay close attention to changes in the blood levels of important drugs they are taking and adjust accordingly under a doctor’s supervision. Again, I doubt they will have a supervising physician when buying it from non-pharmacies.

Suppose a patient is taking chemotherapy and CBD. The same dose of chemotherapy may produce high blood concentrations of the chemo drugs, and that could be fatal and not effective. The same thing could happen with an epilepsy patient. The interaction would change the effectiveness of the seizure medication.

Evidence suggests that CBD can either increase or decrease the breakdown of other drugs, depending on the drug and the dosages used. The references for that statement are on page 73 of the book called CBD by Leonard Leinow and Juliana Birnbow, which is incidentally a great book to read about CBD.

Drug interactions are especially important to consider when using life-saving drugs, drugs with narrow therapeutic windows, or medications with major adverse side effects.

The list below does not necessarily contain every medication that could be affected by CBD, and not every medication in each of the categories listed in the book causes the interaction. For this reason, don’t take CBD as an alternative medication, or dosage adjustments will be needed. I don’t know what our governor and legislature were thinking when they passed the law without considering the above information. I will list some of the drugs that use the Cytochrome P450 System. As already stated, this is only a partial list:

- Steroids

- HMG CoA reductase inhibitors

- calcium channel blockers

- antihistamines

- pro kinetics

- HIV antivirals

- immune modulators

- benzodiazepines

- anti-arrhythmias

- antibiotics

- anesthetics

- antipsychotics

- antidepressants

- antiepileptics

- beta blockers

- PPIs

- nSAIDs

- angiotensin II blockers

- oral hypoglycemic agents

- sulfonylureas

One’s total body makeup is a moving target, and attempts at cannabis therapy without clear indications, which are very few, without an expert physician, can be very dangerous. Although it is always a good idea to consult a doctor for diagnosis and guidance, the fact is that very few practitioners are skilled in the nuances of cannabis therapy, strain selection, CBD ratio selection, and dosage guidance. In addition, each person has a distinct body weight and chemistry as well as unique sensitivity or tolerance to cannabinol products like CBD.

The Main Lie: Marijuana Is Not Harmful

About 12% of Americans are addicted to alcohol, about 9% of adults are addicted to marijuana, and 17% of adolescents will develop an addiction to marijuana.

Such problems are much more likely to arise if someone uses marijuana daily or nearly every day, or if someone begins regular use as an adolescent. Occasional marijuana use is less likely to be harmful in the same way that drinking in moderation in some people does not seem to lead to habituation or addiction. But people smoking multiple times a week usually leads to regular use. Daily or near daily use often leads to marijuana addiction, as already mentioned. The Diagnostic and Statistical Manual of Mental Health Disorders (DSM-5) details how Marijuana Use Disorder often causes major problems in many important areas of a person’s life, such as school, work, or relationships. Right now, about 2.7 million Americans are addicted to marijuana—and could benefit from treatment.

But rather than tackling this issue, state legislatures in places like Indiana are promoting medical marijuana in various guises, including CBD oils.

The political push will be hard to fight. Major government and corporate leaders are backing leading marijuana companies to make a lot of money. Especially, with Canada legalizing marijuana, it will be difficult to resist changes in our national laws. It’s the money.

Catastrophic events, overdoses, assaults, and the rest are what often lead people into treatment for the “hard drugs.” They may say no one ever overdosed on marijuana, but I don’t agree. Marijuana and CBD can be the cause of medical harm or death through the inactivation, at least in part, of the Cytochrome P450 enzymes.

I do some teaching and wellness coaching at major factories, and about 70% of the workers I meet smoke cigarettes. One of these workers once said to me, “You realize Doc, a significant number of the people here are also smoking marijuana.” The company actually has a policy of unannounced drug testing, which means some workers are going to lose their jobs. The reason is that while alcohol and opiates are detoxified in a matter of hours, it takes days or weeks to detoxify cannabinoids. Many would lose their employment, and job terminations involve walking you out the door. Worse, other companies may not hire you because of your history of testing positive for illicit substances.

Scientific research shows that regular marijuana use affects the ability to think, can increase feelings or anxiety and depression, and can likewise increase the odds that one will develop psychotic disorders such as schizophrenia.

Your brain cannot perform the way it’s supposed to when you use marijuana. The main active ingredient in the drug is THC, which produces the high. When you heat CBD, you can convert some of that into THC. The method is readily available on the internet. So, we can easily see how dangerous it is to sell CBD across our state, without age restriction, without warnings about how it is metabolized and interacts with the medications you’re already taking.

The potency of the products sold has increased tremendously in the last 10 years, making them still more dangerous. THC affects your body by plugging into the microscopic sockets in the brain called “cannabinoid receptors.” Many of these receptors are found in the parts of the brain that control thinking, concentration, coordination, and memory. The short-term effects of marijuana use include increased heart rate, slow reaction time, car accidents, and balance problems with increased falls.

The long-term effects of regular marijuana use are even more troublesome. Regular marijuana use hinders frontal-executive brain function, the ability to perform tasks that require complex thinking. For example, suppose you’re riding a bicycle or motorcycle, and you have smoked marijuana in the last hour: your judgment will be severely impaired, as well as your balance.

Those who began smoking marijuana regularly before age 16 perform especially poorly on cognitive tests. Marijuana use at any age can cause serious problems but use among those age 16 or younger is especially worrisome, because of the increased likelihood of addiction and the potential long-term consequences on brain development. The results have been demonstrated in functional MRI scans. I have personally reviewed them. The holes in the brain do not repair themselves. You can take a brilliant child and convert her to an average child. You can take an average child and convert him to a below-average child.

Studies have even shown that regular marijuana use causes your IQ to drop. A recent study by Duke University followed more than 1000 New Zealand residents over their lifetimes, measuring their scores on IQ tests at ages 13 and 38. This proves that regular marijuana use beginning in the teenage years leads to a decline in IQ. Those who use marijuana regularly for years experience about an 8-point drop in their IQ scores over a 25-year period. The science is out there and we have to accept that before passing legislation that legalizes cannabinol products.



You can see Dr. Kachmann's Access TV Shows Mondays at 6:30 pm or Wednesdays at 6:00 pm on Comcast channel 57. 

You can hear him on the radio at 95.7 WELT on Tuesdays at 12:00 pm and Thursdays at 8:00 am.

You can attend one of his monthly evening lectures at the Kachmann Auditorium in Lutheran Hospital (check Facebook for event details).

Or you can visit him after 9:00 am on Fridays at Three Rivers Pharmacy on North Anthony, where he gives free consultations.

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