CBD does not work the way THC does. THC switches on a receptor in the brain called CB1. CBD hardly binds to that receptor at all and instead appears to act on many different targets, none of which has been proven to explain its effects in people.1
That uncertainty matters. Marketing often presents CBD’s mechanism as settled science (“it balances your endocannabinoid system”). The honest position is that scientists have a long list of possibilities and few firm answers.
What is the endocannabinoid system?
The endocannabinoid system is a signalling network the body uses to fine-tune activity in nerves, the immune system and other tissues. It has three parts:2
- Receptors. CB1 is found mainly in the brain and nerves. CB2 is found mainly on immune cells.
- Endocannabinoids. These are cannabinoid-like molecules the body makes itself. The two main ones are anandamide and 2-AG.
- Enzymes. These build the endocannabinoids and break them down. One of them, called FAAH, breaks down anandamide.
The system was mapped relatively late. The first cannabinoid receptor was identified in 1988 and anandamide four years later.3 Much about it is still being worked out.
How is CBD different from THC at the receptor?
THC produces its effects by activating CB1. In mice, THC caused the full set of changes seen when CB1 is switched on. CBD caused none of them.1
In binding tests, most studies find no measurable response from CBD at CB1, and CBD also shows low affinity for CB2.1 This is the simplest explanation for why CBD is not intoxicating. See CBD vs THC and Does CBD get you high?
More recent work suggests CBD may be a “negative allosteric modulator” of CB1. In plain terms, it may attach to a different spot on the receptor and turn down the receptor’s response to THC and similar compounds, without blocking it outright. The World Health Organization’s review describes this as a suggestion from recent evidence, not an established fact.1
What else does CBD act on?
Researchers have proposed more than 65 molecular targets for CBD.4 The main candidates are:
| Proposed target | What CBD appears to do in the laboratory |
|---|---|
| Anandamide | May raise levels by blocking its reuptake and slowing its breakdown1 |
| Serotonin 5-HT1A receptor | Enhances activity1 |
| Glycine receptors | Enhances activity1 |
| Adenosine | Slows its uptake by cells1 |
| GPR55 receptor | Blocks it1 |
| TRPV1 channel (the receptor that responds to chilli) | Activates it1 |
Two cautions apply to this list.
First, the World Health Organization’s review says plainly: “It is not clear which, if any, of these mechanisms are responsible for any of CBD’s potential clinical or other effects.”1 Even for epilepsy, where CBD is a registered medicine, the prescribing information states that the precise mechanism in humans is unknown.5
Second, a result in a dish of cells often needs concentrations far higher than a person reaches after a dose. A long list of targets is not a list of benefits. Our page on how we grade evidence explains why laboratory findings rank lowest.
Does CBD “boost” or “balance” the endocannabinoid system?
This is the most common claim, and it stretches the science. Laboratory studies suggest CBD may slow the removal of anandamide, but reviews are not consistent on whether this happens in humans.12 “Balance” is a marketing word. It is not something the clinical trials of CBD have measured.
What happens to CBD after you take it?
How CBD moves through the body explains several practical points about dose, timing and safety.
Absorption is poor and erratic. Swallowed on an empty stomach, about 6% of a dose reaches the bloodstream. The rest is lost, largely because the liver breaks it down before it circulates.1 See CBD bioavailability.
Food changes the dose you actually get. A high-fat meal raises the peak blood level about five times and total exposure about four times compared with fasting.5 See taking CBD with food.
It is slow in and slow out. After a swallowed dose, blood levels peak at about 2.5 to 5 hours. With repeated dosing the half-life (the time for the blood level to halve) is 56 to 61 hours.5 CBD is fat-soluble and may build up in body fat.1 See how long CBD stays in your system.
The liver does the work. CBD is broken down mainly by two liver enzymes, CYP3A4 and CYP2C19.1 CBD also slows several of the enzymes that process other medicines.5 This is why it can raise the blood levels of some medicines, and why some medicines change CBD levels. See CBD drug interactions and CBD and the liver.
Does CBD change the effects of THC?
It is often said that CBD “takes the edge off” THC. The evidence is mixed. Some studies have found that CBD reduces or opposes some effects of THC.1 But in a controlled study of 31 cannabis smokers, taking 200, 400 or 800 mg of CBD by mouth beforehand did not reduce the high, the heart rate rise or the appeal of smoked cannabis.1
CBD should not be relied on to cancel out THC. This matters for driving: a product that contains both still contains THC.
What this means in practice
- CBD’s lack of a high has a solid explanation: it does not activate CB1.
- Beyond that, the mechanism is an open research question. Be wary of any source that explains confidently how CBD “works” for a particular condition.
- How well CBD works for a given condition can only be settled by trials in people. Those are summarised in the conditions section.
- The way the body absorbs and clears CBD has real consequences for dose and safety, which is one reason a prescriber sets the dose. See the CBD dosage guide.
Footnotes
-
World Health Organization, Expert Committee on Drug Dependence. Cannabidiol (CBD) critical review report, 2018. https://cdn.who.int/media/docs/default-source/controlled-substances/whocbdreportmay2018-2.pdf ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13 ↩14 ↩15 ↩16 ↩17
-
Review of the endocannabinoid system and cannabidiol pharmacology. PubMed Central. https://pmc.ncbi.nlm.nih.gov/articles/PMC10096752/ ↩ ↩2
-
Crocq MA. History of cannabis and the endocannabinoid system. Dialogues in Clinical Neuroscience, 2020. https://pmc.ncbi.nlm.nih.gov/articles/PMC7605027/ ↩
-
Review of the molecular targets of cannabidiol. PubMed Central. https://pmc.ncbi.nlm.nih.gov/articles/PMC7652785/ ↩
-
Epidiolex (cannabidiol) oral solution, United States prescribing information. DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bf27097-4870-43fb-94f0-f3d0871d1eec ↩ ↩2 ↩3 ↩4
Common questions
What is the endocannabinoid system?
It is a signalling network found throughout the body. It is made up of receptors called CB1 and CB2, cannabinoid-like molecules the body makes itself (anandamide and 2-AG), and the enzymes that build and break those molecules down.
Does CBD bind to cannabinoid receptors?
Only weakly. Laboratory studies show CBD has low affinity for both CB1 and CB2 and does not activate CB1 the way THC does. It may change how the CB1 receptor responds to other compounds.
Do scientists know how CBD reduces seizures?
No. The official prescribing information for the registered CBD medicine says the precise way it reduces seizures in humans is unknown. Several mechanisms have been proposed.
Does CBD boost the body's own cannabinoids?
Possibly. Laboratory work suggests CBD may slow the removal of anandamide, one of the body's own cannabinoids. Reviews do not fully agree on whether this happens to a meaningful degree in people.
This page is general information, not medical or legal advice. Laws and evidence change; we show the date we last checked the facts at the top of every page. Talk to your doctor or pharmacist before starting, stopping or changing any medicine.
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