Honey Moon Effect, Tolerance, Reverse-Tolerance and Cross-Tolerance

Published by Rhonda Moeller on May 12, 2019May 12, 2019

So you have been using cannabis for yourself or your child, whether that is high CBD or high THC or any ratio in between, and you feel that it is no longer working as it once did.  Are you going crazy?  How did it work so well for weeks, even months, and now it is not working like it used to? You are starting to wonder if you imagined it all.  Doubt creeps in, and you begin to second guess everything. Is that brand of the product no longer any good?  Was the new bottle you purchased mislabeled?  How did it go from amazing effects to almost no effect so quickly?

Well, you aren’t crazy.  The product you purchased is probably just fine.  The amazing effects you first saw from your cannabis product can and will come back once you understand what is happening.

If you are starting cannabis and you see the first thing you try working great for a few weeks to a few months and then it no longer works well, what you are seeing is called the honeymoon effect. This type of effect, as described by The Epilepsy Foundation, is seen in some individuals where the effectiveness of a new medication tends to wear off over time after doing very well for some weeks or, more often, some months. Many patients who are said to have “medically refractory epilepsy” are those for whom the honeymoon effect is most prominent. We also see this same phenomenon when families are just starting to use cannabis to help manage the symptoms of autism.

But if you have been using cannabis for a bit longer, more than about three months, and efficacy begins to wane, that is what we call tolerance. This type of tolerance tends to be seen more so with THC than CBD. The receptors THC binds to become less dense with consistent prolonged use, and these receptors are no longer available to be activated. In our support group of families, those using primarily THC have found that tolerance often develops within weeks to a few months of starting a particular product or strain. Doing a quick google search, you can find many other articles describing tolerance to cannabis, THC in particular.

If you are using CBD primarily and see that the product you are using is no longer effective, that has been described by Dr. Bonni Goldstein as reverse-tolerance. Reverse-tolerance is also called drug sensitization, where less product is needed overtime to get the desired effect. We see this occurring often in our support group of families, usually after 6-7 months of using the same product(s). There was a recent study done using a 20:1 CBD to THC product where 25% of the patients developed a tolerance after an average of 7 months of use. The article describes a tolerance to either the CBD or the small amount of THC used. Upon discussing this article with Dr. Bonni Goldstein, she insisted that these researchers don’t realize it was a reverse-tolerance they were seeing and that they could avoid that type of tolerance by following the tips mentioned below.

There is one other form of tolerance that we often see with our families, and that is cross-tolerance. Cross-tolerance is defined as resistance to the effects of one substance because of exposure to a pharmacologically similar substance. Research has shown a possible cross-tolerance between alcohol and cannabis and psilocybin and cannabis as well as cannabis and barbiturates, opioids, prostaglandins, and chlorpromazine. Families who have children or adults using large amounts of pharmaceuticals have reported that they often need larger doses of cannabis vs families who have not used pharmaceuticals. Once they are weaned off these other medications, it often takes months to years for this type of tolerance to dissipate, and they begin to see that the therapeutic cannabis dose is much lower than when they first started.

From working with families for a few years, we have seen it all and we have seen families try various things to make cannabis work well again once it no longer works like it first did. The trend that we have seen with successful families is the following.

1. Don’t give up: As easy as that sounds, it is often difficult to not throw in the towel. But often families who have seen the effects of cannabis working well, want that success again and are willing to try everything to get it back.
2. Honeymoon Effect: If you think you have experienced what is known as a honeymoon effect, the best thing to do is to understand that you can get back to the success you once saw but what initially worked for a few weeks to months will probably not work well again. In this case, it is often best to start from scratch and begin the trial and error process. One example from the support group is a family who found success with a 3:1 ratio of CBD to THC for about 3 weeks. This was the first ratio of cannabinoids that worked well for their child. After 3 weeks, the success they saw was no longer there. Going back to the drawing board, they started their research again and tried a few different products and ratios until they found a ratio of cannabinoids and dose that worked well again. This new ratio was not close to the 3:1 they used initially, but they were able to use this new set of products for close to a year before needed to readjust again.
3. Tolerance to THC: A majority of people using cannabis experience this type of tolerance. You can continue to up the dose, but best trick we have found is to take a break for 48 hours (called a “reboot” or “cannabis holiday”) or to switch strains/products. Often switching to a new strain/product is enough to make it work well again. This is also why having a few products on hand that work well is essential for long term success.
4. Reverse-Tolerance to CBD: Although this takes longer to happen, it is sometimes a blessing in disguise especially if you need to lower the effective dose due to cost. The same tricks mentioned for tolerance to THC work here too, except when you begin dosing CBD again, you often need a lower dose of CBD. Families using CBD are often instructed to start dosing again at about 50% to 75% of the last dose and if needed, titrate up to find the new therapeutic dose needed. It is often lower than what was used previously.
5. Cross-Tolerance: With cross tolerance, there is no trick around this, unfortunately. People just need to be aware when starting cannabis that if they have used pharmaceuticals long term, they MAY need to use larger doses vs others with similar conditions and that is perfectly okay. Once they have been able to wean off of those pharmaceuticals with their doctor’s assistance, the dose of cannabis needed often drops over time. One adult child who had used heavy doses of pharmaceuticals most of his life was noted using over 200 mg of THC when they first began using cannabis. A few years after they weaned off all of the pharmaceuticals, they are now using a much smaller dose of THC, approximately 50 mg. They may need to continue to monitor and adjust that THC dose down as more time passes.

Long term success is achievable with cannabis. There are possible pitfalls along the way, which can be confusing and overwhelming for people just beginning on this journey. Once you understand these potential pitfalls and how to work around them, the success seen can be life-altering, and in an amazing way.

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