Sometimes more is definitely not better

This study focused on the variations in effects among different individuals taking similar cannabinoid medicines and doses. It was a review study published in March 2023 in the journal Molecules.

The main takeaway from this research is probably that different patients and patient conditions responded very differently to low and high doses of cannabinoids. When this type of variation in effects is based on dosage, the medicine is called Biphasic - a low dose has one effect and a high dose can have the opposite effect. It is also called hormesis by scientists.

Discussed are the different administration methods as well as the factors that contribute to the individual variation in effects and bioavailability of cannabinoids. To determine the optimum cannabinoid doses that provide maximum health benefits with minimum toxic effects, the following factors contribute:

  • exposure factors - delivery route, duration, frequency, and interactions with food
  • individual factors - age, sex
  • individual susceptibility factors - each individual's unique biochemistry: genetic polymorphisms of cannabinoid receptor gene, N-acylethanolamine-hydrolyzing enzymes, THC-metabolizing enzymes, and epigenetic regulations

There is significant technical analysis in the article, especially in the areas of exposure and susceptibility factors. It is a good overall primer on bioavailability and human biochemistry, and demonstrates that we all have different internal capabilities when it comes to processing and utilizing cannabinoid medicine.

In the authors' words:

different people may have distinct optimum dosages of cannabinoids, and the toxic doses can be largely varied

Numerous reports demonstrate the biphasic effects of ∆9-THC and other cannabinoid agonists, in which low and high dosages commonly induce opposing effects

Cannabinoids can increase neurogenesis at low doses. However, at higher concentrations, neurogenesis is impaired

Low dosages of ∆9-THC produce opposing effects on Sprague–Dawley rats compared to high doses.

high dosages of cannabinoids showed orexigenic (appetite stimulant) effects, whereas low doses had anorexigenic (loss of appetite) effects 


The full text review article is here at