THE PHARMACOLOGY OF CANNABIS

It's the most widely used illegal drug on earth, but very few people understand how it works in the brain, I want to shed some light on one of the most inexplicable highs known to humankind

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Cannabis has an incredibly long history of human use

Carl Sagan once famously suggested that cannabis was the first agricultural product grown, something which archeology suggests is indeed true

The Bible is also contains numerous references to a plant that resembles cannabis

All things considered, it seems that the human brain has evolved alongside the use of cannabis

Therefore it's not surprising that we have a receptor system that cannabinoids fit perfectly, known as the endocannabinoid system

There are two distinct receptors within the system known as CB1 and CB2, they're dispersed in different parts of the body but have similar structures

The two main endogenous molecules that bind to them are anandamide and 2-AG

These endocannabinoids regulate a number of different body processes including appetite, inflammation, immunity, and pain perception

Tylenol actually kills pain by blocking the enzyme FAAH, which breaks down anadamide, cacao contains compounds that function similarly as well

As most people are aware, THC is considered the primary active constituent of cannabis

Interestingly it's actually a lipid, because of this it can be stored in fats cells which is why you can sometimes fail a drug test weeks after quitting smoking

THC only partially activates CB1/2 receptors, but the higher concentration of it leads to psychoactive effect

One of it's primary actions is moderately lowering levels of the messenger molecule cAMP (opiates have a similar effect) which may be how THC can reduce pain/excitation

Because of this, at lower doses THC is usually very relaxing/sedating, but at higher doses this effect changes

Many have had the experience of getting "too high" at some point, this is a result of something called retrograde signalling

One of the functions of ECs is to prevent excitatory/inhibitory signals from firing at the same time, usually by blocking inhibitory signals, since THC is not as selective as ECs are this results in excitatory signals in different brain regions firing at the same time

In simpler terms lower doses increase GABA while higher doses increase Glutamate

THC also seems to block leptin (the hormone that tells you when you're full), and as a result may have some ability to lower insulin levels, both of which contribute to the "munchies"

CBD is the other primary constituent of marijuana, it is what's known as a negative allosteric modulator of the CB receptors

Think of it as a brake system, it slows down overactivation caused by THC, this is why high-CBD strain are often less anxiety inducing

CBD is neuroprotective (as are ECs), and may have some ability to prevent neurodegenerative disorders

It also has a protective effect on insulin producing cells which many help prevent diabetes, and prevents excess inflammatory cytokine release

It may also reduce autoimmunity by shifting the immune system towards the Th2 mode of expression

Interestingly it has also been shown to inhibit FAAH as well, increasing the concentration of anandamide in the brain

Both THC and CBD also activate a receptor called TRPV1

TRPV1 is fascinating because it's actually responsible for the sensation of hot/cold (capsaicin binds to it which is what makes food spicy), it's activation causes the release of endorphins and blocks inflammation

Activation of CB receptors has also been shown to activate a number of pathways that induce apoptosis (programmed cell death), apoptosis is what keeps most cells from growing into tumors, because of this many compounds in cannabis have been researched for anti-cancer potential

The psychologically addictive effects of cannabis result from a pairing opiate and CB receptors that occurs in some parts of the brain, activating one results in some crossover activation of the other, as well as the release of endorphins from TRPV1, both produce reward/euphoria

Cannabis use also downregulates endocannabinoid production in the brain, creating tolerance to some of its effects over time, the system may take some time to bounce back after long term use hence why some people feel mildly "off" after quitting

Overall though cannabis contains over 400 compounds, and 50+ active cannabinoids, many of these lesser compounds have not been researched, but a few have

These include:

THCV: has been researched as a possible seizure preventative, may stimulate bone growth

THCA: the "inactive" form of THC, may prevent seizures, found in raw cannabis

CBC: may inhibit cancer cell growth, may promote bone growth, anti-inflammatory

Etc...

The idea that a strain that smells better to you will result in a high you like more actually has scientific backing

This is a result of a class of compounds called terpenes responsible for the smells of most plants/herbs

Terpenes actually have mild psychoactive effects that can synergize with the effects of cannabis some of these terpenes include:

Linalool: also found in lavender, sedative and antispasmodic

Myrcene: also found in many kitchen spices, enhances the sedative effects of cannabis

a-Pinene: also found in pine trees, a mild acetylcholinesterase inhibitor, promotes memory + cognition

b-Caryophyllene: also found in black pepper/cloves, also activates the CB receptors

Limonene: also found in citrus fruits, has anti-anxiety and anti-depressant effects

Cannabis is a fascinating plant with a very complex range of effects on the human body, it's being researched more and more, but this covered just about everything we know at this point

If you have any questions feel free to DM me or reply to this

Thanks for reading