Medical Research

CBD, THC, & The Tangled Web They Weave

Written by Loren Devito, PhD

Understanding how these compounds interact in the brain

It seems like THC is getting left in the dust these days. With the booming CBD industry showing no sign of slowing down, THC is taking a back seat to the popularity of this cannabinoid. And, perhaps, for good reason.

Medical cannabis patients (and many consumers) want to benefit from the effects of the plant without their days being disrupted by the THC “high.” And so there are plenty of isolates now available of the cannabis- or hemp-derived nature to fulfill this need. Not to mention, CBD on its own has been reported to possess a host of healing properties. So, is it time to say “see ya later” to THC? Not so fast.

The “entourage effect” posits that the combined efforts of all cannabinoids, including THC (as well as many lesser known cannabinoids and terpenes), carry greater effects than any compound in isolation—a chemical gestalt, if you will. So no one chemical should thus be hoisted above another in a tug-of-war for dominance. Instead, harmony can be achieved with these chemicals working together.

So how then do CBD and THC, for example, affect each other in the brain?

Since cannabis-derived medications are approved (or soon-to-be approved) for many different types of neurological conditions, this question is both of interest and relevance to the clinical study of cannabis.

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  • THC binds to the cannabinoid receptors (CB) 1 and 2 in the brain
  • Through its effect on CB1, most of the signals it mediates are inhibitory; however, CB1 activation can increase levels of certain chemicals like dopamine, which is associated with conditions like schizophrenia and Parkinson’s disease. [1]


  • While CBD also binds to CB1 and CB2, it does not activate them quite like THC. Instead, CBD works at lower concentrations. [1] At these levels, it can regulate CB1 function without directly affecting the receptor’s active state (called inverse agonism); it may also similarly affect CB2.
  • Additionally, CBD affects a wide range of other receptors, including adenosine, serotonin, and TRPV1, which could explain its effects on immune function, mood, and pain, respectively. [2]

Combined Effects

Due to these different pharmacological actions, it has been suggested that CBD may “tame” the effects of THC in the brain. This notion has some significant implications, since THC, as noted above, is associated with schizophrenia (although a causative link is controversial, there is evidence of an association). And being able to mitigate some of these effects by including CBD in with THC could be very helpful.

But how exactly might this “taming” occur in the brain?

A recent study looked into CBD-THC interactions in a part of the brain important for memory called the hippocampus. [3] Researchers from the University of Western Ontario delivered either THC and CBD to the hippocampus in an animal model and looked at the effects on certain behaviors as well as levels of dopamine. They found that THC-induced changes in dopamine and certain behaviors were reversed after CBD administration. Additionally, they identified a signaling pathway that played a critical role in mediating these effects.

“For years we have known that strains of cannabis high in THC and low in CBD were more likely to cause psychiatric side-effects,” said Steven Laviolette, PhD in a press release. “Our findings identify for the first time the molecular mechanisms by which CBD may actually block these THC-related side-effects.”

While these findings are certainly fascinating, we don’t yet have enough evidence to say which types of products would work best for each person. However, it is always important to carefully read packages so you know how much THC, CBD, and other cannabinoids, as well as terpenes, are contained in every product, as they all exert individual and combined effects that can greatly influence your experience.



  1. Pertwee, R.G. “The Diverse CB1 and CB2 Receptor Pharmacology of Three Plant Cannabinoids: Delta-9-tetrahydrocannabinol, Cannabidiol and Delta-9-tetrahydrocannabivarin. Br J Pharmacol, vol.153, 2008, pp. 199-215.
  2. Burstein, S., “Cannabidiol (CBD) and Its Analogs: A Review of Their Effects on Inflammation.” Bioorg Med Chem, vol.23, 2015, pp. 1377-1385.
  3. Hudson, R., et al., “Cannabidiol Counteracts the Psychotropic Side-Effects of Δ-9-Tetrahydrocannabinol in the Ventral Hippocampus Through Bi-Directional Control of ERK1-2 Phosphorylation.” J Neurosci. 2019, epub.


Image Credit: CBC News

About the author

Loren Devito, PhD

Loren DeVito, PhD is a neuroscientist and science writer with expertise in cannabis science and medicine. She is committed to communicating evidence-based information about cannabis and its healing properties. Learn more about her work at