We get asked a lot of questions about
cannabis, and one of the most commonly asked-about cannabinoids is cannabidiol
(CBD). There’s been a lot of focus in the media on this particular cannabinoid,
and understandably so – it’s very unique and has a lot of interesting
medical potential. Here’s a simple breakdown of what CBD is and how
it can be used for various types of pain, chronic or otherwise.
- CBD is one of up to 144
cannabinoids produced by the cannabis plant. The cannabis plant also contains
up to 212 terpenes.
- CBD is the second most-abundantly
produced cannabinoid in the cannabis plant after tetrahydrocannabinol (THC).
- CBD’s chemical formula is C21H30O2
– the formula and the way in which the compound binds makes CBD a partial
“mimic” of the body’s own endocannabinoids, the neurotransmitters anandamide (C22H37NO2)
and 2-Arachidonoylglycerol (2-AG, C23H38O4).
- The acidic form of CBD is
cannabidiolic acid (CBDA). CBDA also has anti-inflammatory effects, and may be
used in combination with CBD to enhance its effects (the “entourage effect”).
- When CBDA is
decarboxylated (i.e. it loses a carboxyl group by application of heat or
- In the cannabis plant,
cannabigerolic acid (CBGA) is the precursor cannabinoid to THC and CBD. Both
THC and CBD are produced by the same metabolic pathways. The only difference is
How does CBD work?
- The precise mechanism of
action of CBD is still unknown.
- Some research suggests
that the pharmacological effects of CBD are produced by the inhibition of the
enzyme, fatty acid amide hydrolase (FAAH), which increases that amount of
anandamide available in the body.
- CBD is metabolized in the liver and gut by cytochrome P2C19 (CYP2C19)
and cytochrome P3A4 (CYP3A4) enzymes, as well as UDP glucuronosyltransferase
(UGT) gene types UGT1A7, UGT1A9 and UGT2B7 isoforms
- CBD desensitizes the liver enzyme
- CBD is an indirect
antagonist of the cannabinoid receptors 1 and 2 (CB1 and CB2) – one reason why
CBD may affect the immune system and inhibit cytokine production, which reduces
- CBD is an antagonist of
the G protein-coupled receptor, GPR55.
- CBD is a partial agonist
of the serotonin receptor, 5HT1A – one reason why it may help with depression
and anxiety, as well as preventing nausea.
- CBD has also been shown to be an
allosteric modulator of the mu- and delta- opioid receptors – one reason why it
may be a painkiller/pain distractor.
- CBD may help regulate calcium,
potassium and sodium ion channels in the body’s cells – one reason why CBD may
help control neuronal excitability and be useful for epilepsy and neuropathic
- CBD and its acidic precursor,
cannabidiolic acid (CBDA) also selectively inhibits cyclooxygenase (COX)-2
activity – a reason why CBD may help beat pain and kill cancer cells.
- CBD also interacts with dopamine,
the body’s “reward” neurotransmitter, although precisely how and in what way
still needs to be determined. This interaction may be another reason why CBD
may help beat pain, regulate mood disorders and be useful as an antipsychotic,
as well as help beat drug cravings.
- CBD, as well as the cannabinoid
cannabidivarin (CBDV), desensitize the
receptor potential cation channel subfamily V member 1 (TRPV1). This may be
another reason why CBD can help control neuronal excitability and inflammation.
CBD get you “high” or “stoned”?
- CBD is not as psychoactive as THC.
- CBD does have distinct
pharmacological effects, so could be said to be “psychoactive”, but to a much
lesser degree than THC and with quite different effects.
- Whilst many do not report a
psychoactive effect in the same vein as THC, many do report a “relaxed”
- High doses of CBD may produce an
“energetic” or “wiry” effect in some people, and so cause insomnia in those who
are prone to it.
THC – how they interact
- There is some suggestion that high
doses of CBD can counteract or balance the effects of THC
- At the same time, CBD can
potentiate the effects of THC by increasing CB1 receptor density.
- There is also some suggestion
that, in order for CBD to be truly effective for pain, it must be used in conjunction with THC, even non-psychoactive
amounts. he reasoning behind this is the THC “allows” CBD to cross the
blood-brain barrier. Whether this is entirely true, or whether it is true for
some and not for others, remains to be seen.
- When combined in an equal ratio
(CBD:THC 1:1), the psychoactive effects of THC are diminished significantly for
- High CBD:THC ratios (e.g. 20:1)
generally have little psychoactive effect.
- A THC:CBD ratio of 1:0 (so all
THC) will have significant psychoactive effect. However, the effect may not
necessarily last very long due to the rapidity with which THC is broken down in
- THC:CBD ratios of 2:1 and 3:1 will
likely produce psychoactive effects, perhaps of less intensity than a 1:0
ratio, but for a longer period of time.
- Some people and some conditions
may require higher amounts of THC in order to effectively beat pain.
- Some people may use high CBD
ratios for the daytime when being able to function is key, and higher THC
ratios at nighttime to help aid with sleep and to relax and distract from pain.
- Like THC, CBD’s actions are also
influenced by the plant’s other cannabinoids and terpenes. THCV, CBDV, CBDA,
THCA, myrcene, linalool, limonene, pinene, beta-caryophyllene and many more
cannabinoids and terpenoids can determine the effect CBD has to some degree.
Precisely how these combinations work together and separately still needs to be
there any potential side-effects when using CBD?
Whilst CBD is generally well-tolerated by most
people, just like any other medication, it can have side-effects. These
- Insomnia, especially when used in
- Changes in appetite – usually a
decrease in appetite when it comes to CBD, but sometimes an increase.
- As CBD is an immunosuppressant, it
can suppress T-cell function.
CBD interact with other drugs?
Essentially, yes. As noted above, CBD
desensitizes the liver enzyme cytochrome P450 CYP 450), and affects serotonin,
dopamine and vanilloid receptors, meaning it can interact with a number of
drugs and treatment methods. These include:
- Benzodiazepines, which often includes many types of antiepileptic and antiseizure
- Immunotherapy for cancer.
- Some classes of non-steroidal
Here’s some key things to remember about CBD
and using it for pain:
- CBD roughly mimics the
neurotransmitters anadamide and 2-AG, which play a role in the suppression of
- CBD is an indirect agonist of the
CB1 and CB2 receptors.
- CBD also affects other receptors
in the body, including serotonin, opioid, dopamine and TRPV1 receptors, meaning
it can potentially help with emotional, physical and neuropathic pain, as well
as nausea, neuronal excitability and cravings.
- Whilst CBD isn’t psychoactive to
the same degree as THC, it still has a physiological effect, and so is still
technically“psychoactive” or “partially psychoactive”.
- CBD is an immunosuppressant.
- As CBD desensitizes CYP 450, it
may be necessary to taper off and lessen (or in some cases stop taking
entirely) some types of drugs in the benzodiazepine, barbiturate, opioid, NSAID
and immunosuppressant classes.
- High doses of CBD can counteract
some of the psychoactive effects of THC.
- Whilst CBD can act as a “buffer”
to THC to some extent, it can also elongate THC’s effects.
- Cannabinoids of all types,
including CBD, are biphasic. This means it can have different effects at
- Some people and some conditions
may require the intake of THC in order to provide the desired therapeutic
effects – CBD alone may not be effective.
- High doses of CBD may actually
produce a more “wired” and “energetic” effect in some people, as well as
suppress appetite to some extent.