Understanding Cannabinoids

[Ian]

UNDERSTANDING CANNABINOIDS

 

 

The cannabis plant is well known for its psychotropic and medicinal qualities, as well as its unique effect on the human body and psyche. The chemicals or compounds responsible for these effects are known as cannabinoids. They are highly complex in nature and affect the human body in various ways.

 

Cannabinoids are a group of substances that are structurally related to THC (Delta-9-Tetrahydrocannabinol) or molecular compounds that bind to cannabinoid receptors in the human body. The term cannabinoid also refers to a unique group of secondary metabolites found in the cannabis plant, which are responsible for the plants unique pharmacological effects.

 

There are three general types:

 

Phytocannabinoids - compounds that occur uniquely in cannabis plants.

 

Endogenous cannabinoids - produced in the human body and supposedly in other mammals as well.

 

Synthetic cannabinoids - structurally similar compounds, produced synthetically under laboratory conditions.

 

 

 

 

CANNABINOID RECEPTORS

 

There are certain receptors in the human body that the cannabinoids can bind to, called cannabinoid receptors

 

As mentioned before, some of the cannabinoids are endogenous, which means that they are produced naturally inside the human body. Others are exogenous and must thereby be introduced into the body through the consumption of the cannabis plant. No matter which type of cannabinoid in question, they bind to one of two receptors found in the human body.

 

These are currently known as: CB1 and CB2

 

- CB1 receptors are found primarily in the brain. They are also found in both the male and the female reproductive systems. CB1 receptors account for the euphoric and anticonvulsive and relaxing effects of cannabis.

 

- CB2 receptors are almost exclusively found in the immune system, with greatest density in the spleen. The CB2 receptors account for the anti-inflammatory and other therapeutic effects of cannabis.

 

 

 

 

Several areas of the brain have high densities of these receptors,

which accounts for the different effects that the drug has on us.

 

 

 

Some of the impact on our nervous system is positive and the stimulus from cannabinoids can counteract the negative effect of certain medical conditions. There are however also some adverse effects that arise from long time use, mainly those affecting the hippocampus and the long term memory. Long-term use can also lead to a psychological condition called psychosis, which is often characterized by loss of contact with reality, resulting in unusual or bizarre behavior.

 

Research has shown that these adverse effects might become permanent when cannabis is used from an early age but other than that, the negative effects seem to be merely temporary and all neural and mental functions will be restored to their original state when cannabis is no longer introduced into the nervous system.

 

Although cannabis is a relatively harmless drug compared to some of the legal alternatives, it should not be disregarded that it may cause problems after long-time or chronic use.

 

 

 

 

TYPES OF CANNABINOIDS

 

 

There are at least 80 known cannabinoid compounds that have been isolated from the plant.

 

THC (Delta-9-Tetrahydrocannabinol), CBD (Cannabidiol) and CBN (cannabinol)

are the most prevalent cannabinoids and have received the most attention in scientific studies.

 

Other common and lesser cannabinoids are listed below:

 

- CBG Cannabigerol

- CBC Cannabichromene

- CBL Cannabicyclol

- CBV Cannabivarin

- THCV Tetrahydrocannabivarin

- CBDV Cannabidivarin

- CBCV Cannabichromevarin

- CBGV Cannabigerovarin

- CBGM Cannabigerol Monoethyl Ether

 

Here follows the breakdown of each of the cannabinoids relevant to the biosynthetic chain that eventually leads to the fully realized THC compound, as well as its degradation product.

 

 

CANNABIGEROL (CBG)

 

 

 

CBG is a precursor of higher cannabinoids such as CBC, CBD, THC and there are very small amounts of it in drug strains although it occurs in greater concentrations in hemp. It's a non-psychoactive cannabinoid but it is known for lowering blood pressure and it is also useful for treating mood disorders.

 

 

 

CANNABICHROMENE (CBC)

 

 

 

CBC is nonpsychoactive and it is used as an "energy-storage" compound which is readily converted back to CBG if needed. Some evidence show that CBC may play a role in providing the anti-inflammatory effects of cannabis and that it may also contribute to the overall analgesic or pain killing properties, but further research is needed to verify these assumptions.

 

 

 

CANNABIDIOL (CBD)

 

 

 

Cannabidiol is nonpsychoactive and was initially thought to have no effect on the psycho activity of THC. Recent evidence however show that smokers of cannabis are less likely to experience schizophrenia-like symptoms if there is a higher CBD to THC ratio. Experiments show that participants experienced less intense psychotic effects when intravenous THC was co-administered with CBD. It has been hypothesized that CBD acts as an allosteric antagonist at the CB1 receptor and thus alters the psychoactive effects of THC, resulting in a more easily manageable high.

 

CBD is generally considered to have more medicinal properties than THC. It appears to relieve convulsion, inflammation (and thereby also migraines), anxiety and nausea. That is why strains with a high concentration of CBD is suitable for medicinal use.

 

Although CBD has its own particular medicinal value it is not more important than THC when it comes to treating various afflictions. It is the interaction between the two that gives rise to the effect that sometimes alleviates the symptoms of various medical conditions.

 

CBD has a greater affinity for the CB2 receptor than for the CB1 receptor, meaning that its effect is mostly in the body and not so much in the head. CBD shares a precursor with THC and is the main cannabinoid in low-THC cannabis strains like hemp.

 

Landrace strains, usually of indica heritage, contain higher concentrations of CBD than recreational drug strains, which are usually bred towards a higher concentration of THC. This is the reason why strains containing high ratios of CBD can be difficult to find.

 

 

 

TETRAHYDROCANNABINOL (THC)

 

 

 

 

Tetrahydrocannabinol, also known as delta-9-tetrahydrocannabinol (Δ9-THC), is the primary psychoactive component found in the cannabis plant. It was first isolated by Raphael Mechoulam, Yechiel Gaoni, and Habib Edery from the Weizmann Institute of Science in Rehovot, Israel, in 1964.

 

 

 

This is the main compound that gives rise to the high that is tightly linked with the cannabis plant. It affects several areas of the brain simultaneously and can therefore give rise to an assortment of experiences, ranging from altered perception of time and the self, to feelings of euphoria and relaxation all through the body.

 

Medically, it appears to be analgetic, meaning that it is capable of alleviating even severe pain. It is also known to be neuroprotective, which rules out the possibility of brain damage, which was initially proposed to follow from heavy use of the plant. It has approximately equal affinity for the CB1 and CB2 receptors. By binding to CB1 receptors (the ones in brain) it produces the high that we are so familiar with. That is why the effects of THC is more cerebral, than the effect of CBD, which seems to have a greater affinity for the CB2 receptor.

 

 

 

TETRAHYDROCANNABIVARIN (THCV)

 

 

 

THCV is the propyl homologue of THC and is similar in structure. The propyl cannabinoids have so far been found in some varieties originating from Southeast and Central parts of Asia as well as Africa, Afghanistan, Pakistan, India and Nepal. What are considered some of the most potent marijuana varieties also contain propyl cannabinoids. Some examples include traditional African landrace sativas as well as pure Thai varieties and various hybrids known as Haze.

 

There are no reports on its activity in humans. From animal studies it appears to be much faster in onset and quicker to dissipate than THC. It appears that it's activity is somewhat less than of THC. THCV is known for removing the "ceiling" from the high, giving the smoker the impression that he only gets higher with every passing minute until the effect eventually wears off.

 

 

 

CANNABINOL (CBN)

 

 

 

Cannabinol is the primary degradation product of THC and increases in concentration with plant age. The concentration of this product in the bud is heavily dependent on the time of harvest. Harvesting the bud at a late stage also means that the concentration of CBN in relation to THC will be higher when compared to the peak of THC production.

 

CBN content also increases as THC degrades during storage and with exposure to light and air. It is only mildly psychoactive and can cause "fuzzy head", drowsiness, disorientation and sleepiness in the smoker, properties that can be considered unpleasant in nature compared to the clear high of the THC. Its affinity to the CB2 receptors is higher than for the CB1 receptor, meaning that it mostly affects the body.

 

 

 

THC BIOSYNTHESIS

 

 

In order to fully understand and appreciate the most important cannabinoids, we first have to take a look at how they are produced inside the plant from lesser, precursor compounds.

 

This image has been resized. Click this bar to view the full image. The original image is sized 1024x420 and weights 51KB.

 

 

By looking at this picture we get a better view of the metabolic pathway that leads to the desired psychoactive product called THC.

 

Upon researching how THC is produced in the plant, we came upon two different theories, that we will present here.

 

The first model, on the left, is supported by the scientific community, while the model on the right is based on information provided by some of the most experienced growers and breeders of our own community.

 

The first theory suggests that THC is refined from CBD and that they are linked in a chain as portrayed on the left. These conclusions might be based on the fact that it is possible to turn CBD into THC by bombarding it with ultraviolet radiation.

 

The second theory suggests that CBD and THC are actually not linked at all and that they are produced independently of each other from the shared cannabinoid precursor CBG.

 

The truth might lie somewhere in the middle. It has been suggested that when cannabis is exposed to UVB radiation, a secondary metabolic pathway is activated, effectively doubling the THC output. This is an evolutionary response to the harmful ultraviolet radiation that may cause mutations and other tissue damage in the plant. Studies on marijuana optics suggest that the globular head of the THC trichome binds solar energy and thereby prevents it from harming the plant. If this is true, then both models might be correct. One works all the time and the other kicks in under exposure to heavy solar radiation. More research is needed in order to confirm this theory but the elevated THC content of high altitude strains seems to support it.

 

Admittedly, our knowledge of molecular chemistry is not so advanced that we could make our own conclusions based on the molecular structure of the various cannabinoid compounds.

 

This biological production of the much desired THC compound that has made the cannabis plant so famous, all take place inside something called a trichome. Trichomes are fine outgrowths or appendages on plants that resemble crystal mushrooms in cannabis. Trichomes are not unique to cannabis plants but the psychoactive components that can be found in it are.

 

 

 

These "mushrooms" are in fact stalked, glandular containers of cannabis oil, which matures as it goes through the transformation into THC from lesser cannabinoid compounds.

 

 

 

THE DIFFERENT TYPES OF TRICHOME GLANDS

 

 

Trichomes are fine outgrowths or appendages on plants, also called resin glands. Trichomes can vary in size and structure depending on the plant in question. We are however only interested in the trichomes found on cannabis plants.

 

There are three known types of glands that occur on the cannabis plant.

They are most heavily concentrated on the floral parts of the female plant:

 

 

(Photo by Pistals)

 

 

Bulbous

 

These types of gland are the smallest (15-30 micron across). Anywhere from one to four cells make up the "foot" and "stalk," and one to four cells make up the "head" of the gland. They can be found everywhere on the surface of the plant that is above ground level. Head cells secrete a resin, presumably cannabinoids, and related compounds that accumulate between the head cells and the cuticle.

 

Capitate – Sessile

 

The second type of gland is larger (25 to 100 micrometers) and more numerous than the bulbous glands. They are called capitate, which means having a globular-shaped head. On immature plants, the heads lie flush, appearing not to have a stalk and are called capitate sessile. They have a stalk that is one cell high, although it may not be visible beneath the globular head. These cells secrete cannabinoids and related compounds.

 

 

 

Capitate – Stalked

 

These type of glands appear during flowering and occur especially on the bracts subtending a flower and seed and also small leaves that accompany the flowers. They contain the highest concentration of cannabinoids and can range in size from 150 – 500 microns. The male flowers also have stalked glands, but they are smaller and less concentrated than on the female plant. These resin glands contain the most THC, which is also why they are the most important. Good cannabis plants have mostly capitate-stalked glandular trichomes and in very high concentration.

(The structures pointed out by the red arrow is a cystolith hair that lack the bulbous head of the other trichomes.)

 

In order to determine the dominant type of trichome on your plant, you will need to look at the female flowers through magnification. Although different plants may seem as frosty as the next, it is actually the dominant type of trichome and the concentration in which it occurs that determines the potency of the final product.

 

The capitate-stalked glandular trichome changes color as it matures. Newly formed and immature glands are opaque, glands reaching optimum THC production are cloudy or milky and amber trichomes have already passed their peak. By looking at the trichomes you can also determine the best time to harvest your plants. When most trichomes have gone cloudy and a few amber ones have appeared, the plant is at its peak.

 

 

 

 

INSIDE THE TRICHOME

 

THC and other cannabinoids are produced mostly in one place on the cannabis plant:

inside the heads of the capitate-stalked trichomes.

 

 

 

How it happens:

 

Organelles produced by the plant called Vacuoles - which contain phenols, a chemical compound similar to alcohol and another type of organelle called plastids - containing hydrocarbons called terpenes, make their way up the trichome stalk and combine inside the secretory cavity into a fibrous mat. This concentrated mat is hit by UV-B light waves, causing the creation of cannabinoids. Since all of the psychoactive ingredients are produced inside the trichome, these tiny resin heads have long been sought after by hash and oil makers and can be separated from the plant and harvest in a variety of ways.

 

 

 

Why Trichomes?

 

Cannabis and many other plants have evolved resin trichomes for variety of uses. They protect the plant from UVB light rays, especially Cannabis plant since THC has very good UV-B light absorption. It protects the plant from insects and animals and also provides protection for buds from low humidity and harsh winds.

 

http://www.icmag.com/ic/showthread.php?t=163471

[porcupine]

Thanks Ian. Do you possibly have a comprehensive report on terpenes and terpenoids?

[Ian]

NO sorry, I came across this and thought it would be good match to:

Vapor Temps For Cannabinoids And Medical Properties -

http://www.michiganmedicalmarijuana.org/index.php?/topic/18240-vapor-temps-for-cannabinoids-and-medical-properties/page__p__158290__hl__vapor__fromsearch__1entry158290