What is CBD – How does it work


One of the most popular and interest arousing 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 101

  • 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 oxygen).
  • 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 that CBDA

How does it 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 CYP450.
  • 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 inflammation.
  • 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 pain.
  • 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, transient receptor potential cation channel subfamily V member 1 (TRPV1). This may be another reason why CBD can help control neuronal excitability and inflammation.

CBD Effects

  • 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” feeling.
  • 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.

CBD and THC

  • 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 many people.
  • 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 the body.
  • 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 figured out.

Side Effects

Whilst CBD is generally well-tolerated by most people, just like any other medication, it can have side-effects. These include:

  • Drowsiness.
  • Insomnia, especially when used in high doses.
  • Diarrhea.
  • Changes in appetite – usually a decrease in appetite when it comes to CBD, but sometimes an increase.
  • Fatigue.
  • As CBD is an immunosuppressant, it can suppress T-cell function.

Interactions

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 medications.
  • Barbiturates.
  • Opioids.
  • Alcohol.
  • Immunosuppressants.
  • Immunotherapy for cancer.
  • Some classes of non-steroidal anti-inflammatory medications.

Key Takeaways

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 pain.
  • 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 different dosages.
  • 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.

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