Education

Cannify is constantly researching cannabis and cannabis products. On this page we want to share all known insights with you.
If you have any questions, don't hesitate to contact us.

Help us improve the education pages:
Leave feedback

CBD and THC Interaction – Pharmacokinetics

Cannabis compound interaction, sometimes referred to as the entourage effect, is a very well-discussed topic. One of the best-known examples of cannabinoid interaction is the interaction of cannabinoids delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In this section, we will discuss how CBD interacts with THC in the body, for example what it does to THC’s blood concentration. In the next chapter, we will discuss how they influence each other’s effects. CBD has been observed to mitigate THC’s side effects. This raises the question how the compounds interact in the body. Pharmacokinetics talks about the movement of drugs through the body, and overall, some studies observed that CBD can affect the pharmacokinetics of THC. For example, CBD can increase the THC dose. Here we will give some examples:

Overview of CBD and THC interaction studies

The following overview is a small selection of various studies that looked at THC and CBD interaction. A study with 14 participants showed that when 13.75mg THC and 13.75mg CBD were vaporized, the combination was associated with higher plasma concentrations. For example, the peak plasma concentrations {call-out, text: the concentrations of the drug in the plasma (part of the blood) when they are at their highest} of THC were significantly higher compared to only vaporizing 13.75 THC alone.1 This could have been caused by multiple factors. THC vapor and THC/CBD vapor may have different sensory qualities, leading to the subjects inhaling the vapor slightly differently. The author also explains that CBD inhibits the CYP3A4, CYP2C9, and CYP2C19 isoforms, which are enzymes that are involved in the metabolism of THC. It’s possible that this enzyme inhibition could lead to an increased peak plasma concentration of THC. Another study examined orally administering 10mg THC and 5.4mg CBD, compared to 10mg THC alone. Also, in this study the THC and CBD combination was found to increase plasma concentrations of THC. The author suggests that this is because CBD partially inhibits the CYP2C enzyme that catalyzes the hydroxylation of THC into 11-OH-THC.2 A study with 24 people compared the oral administration of 2.5mg of THC with the oral administration of 2.5mg THC and 1.35mg CBD. In this case, women were found to have higher levels of THC metabolites (11-OH-THC and THC-COOH) than men, when given just THC.3 This also coincided with stronger effects in women compared to men when only THC was administered. In another study, 24 participants were treated with an oromucosal spray of 10mg THC, and another time with an oromucosal spray of 10mg THC and 10mg CBD. The most significant pharmacokinetic effect was the CBD and THC combination causing a delay in the time it took to reach the maximum plasma concentration of THC, compared to just THC. The experienced effects of the THC and CBD combo were milder, and onset slightly delayed. The author suggested that this time delay is probably too small to be important for a patient.4 In a study of 4 participants, 1500mg of CBD was administered orally before 2mg of intravenous THC was administered. The metabolic blood clearance of THC was found to slightly increase with the CBD/THC dose, compared to the pure THC dose.5 This conflicts with other studies that found a greater impact of CBD on the amount of THC in the blood. In a 15-person study, 20mg of THC and 40mg of CBD given orally were associated with increased THC metabolites in urine, compared to what 20mg of oral THC would produce. The authors suggested that CBD may inhibit metabolizing enzymes, explaining a slower onset and longer duration of experienced effects of the THC and CBD combination.6

Discussion

Overall, it appears that giving CBD and THC simultaneously may lead to higher peak plasma concentrations of THC, and create milder effects that last longer, as opposed to what is seen with just THC. An emerging explanation is that CBD may inhibit certain enzymes that metabolize THC. Again, further research is needed on the topic. Some studies, however, have conflicting results about how CBD and THC interact. Also, studies found that there might be a difference between how (fast) males and females break down cannabis compounds. Going forward, there needs to be more scientific research into the pharmacokinetics of the CBD and THC interaction. Administration methods, different ratios of CBD:THC, and the possibility of gender impacting the pharmacokinetics must be all taken into account. Figure 1. Some studies show that when combined, THC and CBD lead to increased and delayed peak plasma concentrations of THC, compared to THC alone. The image gives a schematic representation. References:
  1. Arkell, Thomas R.; Lintzeris, Nicholas; Kevin, Richard C.; Ramaekers, Johannes G.; Vandrey, Ryan; Irwin, Christopher; Haber, Paul S.; McGregor, Iain S. (2019). Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition. Psychopharmacology, 236(9), 2713-2724.
  2. Nadulski, Thomas; Pragst, Fritz; Weinberg, Gordon; Roser, Patrik; Schnelle, Martin; Fronk, Eva-Maria; Stadelmann, Andreas Michael (2005). Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. Therapeutic drug monitoring, 27(6), 799--810.
  3. Roser, Patrik; Gallinat, Jürgen; Weinberg, Gordon; Juckel, Georg; Gorynia, Inge; Stadelmann, Andreas M. (2009). Psychomotor performance in relation to acute oral administration of DELTA9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects. European Archives of Psychiatry and Clinical Neuroscience, 259(5), 284-292.
  4. Guy, G. W.; Robson, P. J. (2003). A Phase I, Double Blind, Three-Way Crossover Study to Assess the Pharmacokinetic Profile of Cannabis Based Medicine Extract (CBME) Administered Sublingually in Variant Cannabinoid Ratios in Normal Healthy Male Volunteers (GWPK0215). Journal of Cannabis Therapeutics, 3(4), 121-152.
  5. Hunt, C.; Anthony Jones, Reese T.; Herning, Ronald I.; Bachman, John (1981). Evidence that cannabidiol does not significantly alter the pharmacokinetics of tetrahydrocannabinol in man. Journal of Pharmacokinetics and Biopharmaceutics, 9(3), 245-260.
  6. Hollister, L. E.; Gillespie, H. (1975). Interactions in man of delta-9-tetrahydrocannabinol. II. Cannabinol and cannabidiol. Clinical pharmacology and therapeutics, 18(1), 80--3.