The cannabis plant had been living, surviving, reproducing, and just plain going about her business for some 60,000 years on Earth before we came along and wanted to use her for medicine, fiber, fuel, or food. In that time, the plant figured out a thing or two about what she needed and how to protect herself from predation by herbivores and insects. Cannabis also figured out how to protect her DNA from the sun’s damaging ultraviolet rays, and she learned how to survive toxically high oxygen levels in the atmosphere and periods of life-threatening loss of water. Any medicinal benefit to us is a cumulative gift from all of our plant ancestors, who figured out how to live on this planet millions of years before we arrived.
Cannabis ruderalis, the wild grandmother of the cannabis we know today, originated in the mountains of central Asia. This plant migrated and gave rise to the two species we now know as cannabis: Cannabis indica and Cannabis sativa. Today, different types of cannabis are classified by their leaf shape — broad or narrow — as well as the levels of CBD and THC present in the plant. In simplistic terms, CBD is the constituent in the plant that has a soothing effect on the body, and THC is the constituent that makes the body feel “high.”
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Whether a cannabis plant is labeled as “hemp” or “drug/marijuana” has to do with its level of THC. “Hemp” is a term created by the government to classify any cannabis that contains 0.3 percent or less THC content (by dry weight). It is cannabis, but with such low levels of THC it cannot get you high. It is a standard imposed by the government, not biological or taxonomical nomenclature. Hemp is cannabis. There are two lineages of cannabis classified as “hemp,” and they are labeled based on the shape of their leaves: narrow-leaf hemp (NLH) and broadleaf hemp (BLH). Hemp is grown for its fiber to make rope, clothing, paper, and building materials. It is also cultivated for food; its seeds are used to make hemp milk, hempseed oil, and hemp nut butter. Hemp is also cultivated for CBD medicine. Most industrial/agricultural hemp varieties have CBD levels of about 8 percent and require processing to create medicine. The 8 percent level will continue to rise as breeders cultivate for plants higher in CBD.
The labels “drug,” “recreational,” and “medical” all denote cannabis flowers with a 0.3 percent or higher level of THC. These imposed terms have underpinnings of judgment and a good-versus-bad paradigm; the culture already has a bias against the word “drug”. What determines the line between recreational and medical use? Is there a line? An increase in quality of life is a common report when working with cannabis; that makes cannabis a good therapeutic tool for any chronic disease. In this book, unless citing scientific nomenclature, I use the term “personal use” to indicate medical or recreational use. The level of THC in personal-use cannabis usually ranges from 14 percent to upward of 30 percent. But again, no matter what the label, all of these flowers are cannabis. And just like with hemp, the lineages of personal-use cannabis are based on the shape of their leaves: narrow-leaf drug (NLD) and broadleaf drug (BLD).
Botanically — not common vernacular — there are two ways of categorizing cannabis: as two species or three. For our discussion, we will use two species: Cannabis sativa and Cannabis indica (Cannabis indica has three subspecies). If you step into a dispensary or talk with your local grower, you will inevitably be asked if you are looking for indica or sativa. People commonly say “sativa” for tall, lanky plants that are energizing and heady and “indica” for short, squat plants that are sedating or provide a body high. While common use of these terms is helpful for figuring out what someone is looking for, it should not be confused with the taxonomical naming by botanists. It can be confusing because what people call “sativa” is actually a subspecies of Cannabis indica: Cannabis indica indica. And for the record, you cannot determine a plant’s sedative or energizing properties simply by looking at it.
|
Scientific name |
Physical attribute |
THC content |
CBD content |
|
Cannabis sativa |
narrow-leaf hemp |
low |
high |
|
Cannabis indica chinensis |
broadleaf hemp |
low |
low |
|
Cannabis indica indica |
narrow-leaf drug |
high |
low |
|
Cannabis indica afghanica |
broadleaf drug |
high |
high |
Narrow-leaf hemp (NLH); low THC, high CBD
Cannabis sativa evolved in the temperate Caucasus Mountains of western Eurasia. This plant is the descendent of cannabis low in THC and high in CBD; it is also called narrow-leaf hemp (NLH). Medicine makers wanting a high-CBD formula can utilize this species.
Cannabis indica evolved in the Hengduan Mountains of Asia. Cannabis indica gave rise to three subspecies: Cannabis indica chinensis, Cannabis indica indica, and Cannabis indica afghanica.
Broadleaf hemp (BLH); low THC, low CBD
Cannabis indica chinensis originated in eastern Asia. It contains low levels of THC and low CBD, so it is bred and used chiefly for fiber and seeds. This subspecies would test low for the two main active constituents and would not be suitable for medicine.
Narrow-leaf drug (NLD); high THC, low CBD
Cannabis indica indica originated in India. It is high in THC and low in CBD, and it is termed narrow-leaf drug (NLD). Cannabis indica indica arrived in the United States in the nineteenth century. These strains, with high THC, were used early on as psychotropic medicines. The effects were described as “heady” and “energizing.” In the recreational cannabis community, this plant is commonly called “sativa” today. This subspecies is typically a light green color, and strains can contain 20 percent or more THC. Over the years, cannabis breeders of NLD species have selected for intoxicating psychoactivity, creating highly psychotropic strains high in THC but very low in CBD. This subspecies is a good medicine when you desire higher THC, terpenes, and other constituents that have not been bred for but may exist in the plant.
Broadleaf drug (BLD); high THC, high CBD
Cannabis indica afghanica originated in Afghanistan. It is high in both THC and CBD and is termed broadleaf drug (BLD). It arrived in the United States in the 1970s. The plant is short, robust, and dark green. This subspecies can contain THC levels of 10 percent and above. It can also be high in CBD. Because CBD and THC both create the resin, plants were bred for their high resin content (to make hashish) and their intoxicating psychoactivity. Selection favored CBD as well as THC, evidenced by the current levels of both constituents in BLD. This subspecies is commonly called “indica” in recreational and medical cannabis dispensary communities and is described as having more of a “body high” and sedative effect, giving the user what is commonly called “couch lock” (because you have difficulty getting off the couch).
To be clear, the botanical classification of cannabis indica and cannabis sativa is not the same as the common use of the terms “indica” and “sativa.”
A narrow-leaf plant in early flower
Cannabis is dioecious: individual plants are usually either male or female. While both sexes produce flowers, male flowers have male reproductive parts that produce pollen while female flowers have female reproductive parts to receive the pollen. Pollinated female plants put a lot of energy into producing seeds, energy that unpollinated plants put into making big, juicy buds with the most potent medicinal potential. Therefore, growers try to remove male plants — along with their flowers and pollen — as soon as sex characteristics appear. Under stressful situations, however, such as extreme temperature or humidity, adverse nutrient or water levels, fluctuating light, or predation, a female cannabis plant can become monoecious and produce both male and female flowers in order to self-pollinate. This is a beautiful survival mechanism: when life is stressful and a plant senses it may have trouble reproducing, she can fertilize herself! (This is great for the wild cannabis plant but not so great for growers.) The plant’s leaves have a classic palmate structure that resembles a hand. Early in the plant’s life, the leaves are arranged oppositely on the stem; as the plant matures, the leaves arrange alternately.
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For medicine, we use all parts of the plant that manufacture cannabinoids and terpenes. The structures that manufacture the cannabinoids and terpenes are called “trichomes.” These sparkly “crystals” are found on the flowers, leaves, twigs, sepals, and perigonial bracts (specialized leaves). The flower itself is prized most highly because it has the most potent trichomes and medicine, but all these parts contain trichomes and thus some medicine-making power. Growers will trim off all non-flower parts when getting ready for selling. These other trichome-containing plant parts are called “trim.” While not nearly as potent as flowers, trim works fine for making medicine. It is not available for sale at dispensaries, but home growers may sell it at a substantially cheaper price than the flowers.
Cannabis is a genus of the Cannabaceae family, of which hops (Humulus lupulus) is the only other member. Interestingly, cannabis was formerly classified with nettles in the Urticaceae family, probably due to the presence of cystolithic and unicellular nonglandular trichomes on both plants. Cannabis and nettles both love to grow in nutrient-rich, well-drained soils with full sun, and both are jam-packed with nutrients, antioxidants, and minerals. Reports of the healing benefits of juicing cannabis leaves are all over the internet. Cannabis-leaf juice is nutrient rich but extremely bitter (as well as illegal in some states). Nettle leaves, on the other hand, are equally nutritious, tastier, cheaper, and legal. Herbalist Lisa Ganora calls cannabis “nettles with benefits.”
One of the ways plants communicate with us is through chemistry. When we smell a rose and feel joyful, we are interacting with the plant via chemicals. When we drink nettle tea and feel fortified, we are communicating with the plant through chemicals. The cannabis plant, with her thousands of variations of chemical profiles, is an apothecary in itself. Each cultivar has a different chemical profile with different healing properties. You could spend a lifetime getting to know just a few cultivars of cannabis and how they work under different conditions. Most people don’t know what cultivar they are working with, and even fewer know the chemical breakdown of the particular cultivar (and therefore what the cultivar may be good for). But the better we understand the chemistry of the plant, the better our ability to make well-informed decisions about what cultivar to use, and what conditions it grows best under, when making and working with cannabis medicinally.
Trichomes are resinous, hairlike glands. They are cannabinoid and terpene factories. They are easily seen with the naked eye; they look like sparkly jewels encrusting the flower. Trichomes cover cannabis flowers and bracts (the small leaves around the flower). They function much like the hair on our arms, which warms us and prevents water loss. Trichomes on the surface and undersides of the flower and bract trap warm and moist air on the surface of the leaf. In essence, they create an ideal micro-environment, protecting leaf, flower, and seeds from ultraviolet radiation in sunlight.
The cannabis plant makes six different types of trichomes. Only three of them produce resin, and we will focus on those. The first of these, called “capitate-stalked,” looks like a tiny mushroom. They are the largest and most numerous, and they produce the most cannabinoid-rich resin. “Capitate-sessile” trichomes look like tiny bulbs; they have stalks, but they are very short. Finally, “bulbous” trichomes look like tiny lightbulbs atop little stalks.
In living plants, trichomes are sensitive and can easily break. They then release their resinous extract, which contains antibacterial and antifungal terpenes and can also trap and kill insects. Trichomes contain chemicals that are bitter, which deters herbivores. Cannabinoids, when released onto the surface of the flower, are necrotic to insects and the leaves, which degrade to expose the voluptuous female flower to the male pollen carried on the wind. That’s right — when the wind blows, plant sperm is flying through the air! The female plant keeps growing the flower, extending and producing sticky resin to catch any of the sperm-containing pollen from the male flower. Once fertilization occurs, the female plant goes about the job of making offspring in the form of seeds.
It’s important to note that trichomes in a dried plant are even more delicate. Anytime you handle a flower roughly by squeezing or dropping it, you break open trichomes, releasing the volatile terpenes and exposing the cannabinoids to oxygen. If you can smell the “cannabis smell,” you’ve broken open some trichomes and released their terpenes. So to make the most potent medicine, handle the plant material as little as possible.
Trichomes function much like the hair on our arms. They trap warm, moist air on the surface of the leaf, creating an ideal micro-environment to protect leaf, flower, and seeds from UV light.
Trichomes are resinous, hairlike glands that produce cannabinoids and terpenes. They look like sparkly jewels encrusting the flower and bracts (the small leaves around the flower). The cannabis plant makes six different types of trichomes; three of them produce resin: capitate-stalked, capitate-sessile, and bulbous.
Capitate-stalked trichomes on the bract — these are the largest and most numerous, and they produce the most resin.
Capitate-sessile trichomes on the underside of a leaf have stalks, but they are very short. Capitate-stalked are seen here with an observable stem.
Bulbous trichomes on a leaf look like tiny lightbulbs atop little stalks. This is a closer view of capitate-stalked trichomes on a female flower.
Trichomes on female flower and bract. Trichomes are delicate, and when broken they release a resinous extract that contains antibacterial, antifungal terpenes and necrotic cannabinoids.
Unpollinated female cannabis flowers are called sinsemilla, “without seed.” They are prized for medicinal use because all the plant’s energy was invested in producing trichomes (which hold the beneficial chemicals) rather than seeds.
For medicinal purposes, we use unpollinated female cannabis flowers, called “sinsemilla,” meaning “without seed.” Sinsemilla flowers are prized because no energy was put into making seeds; instead it was invested into making more trichomes and the chemicals within them.
Cannabis ensures survival of her wisdom and lineage through seed production. Seeds are also an important food source for animals, who happily excrete them along with a nice dose of fertilizer, spreading the plants as they travel. Seeded flowers are useful, of course, for making sure you have something to plant the next season. And seeded flowers can be used for medicine, but they are less potent. In the world of commercial cannabis growers, seeded flowers are undesirable and bring the price of the flower down for two reasons. First, as mentioned, the plant puts energy into making seeds that could have instead made cannabinoid- and terpene-rich trichomes. Second, about 35 percent of the weight of a pollinated flower is seeds. Since seeds are useless to end users of cannabis, they won’t pay as much for seedy flowers. The good news for medicine makers is that once the seeds have been removed, the flowers are only a little less potent than sinsemilla, and you may be able to buy seeded flowers for less — hopefully about 35 percent less.
Seeded flowers can be used for medicine, but they are less potent.
About 35 percent of the weight of a pollinated flower is seeds.
A yellow stamen, “banana,” normally grows inside a male pollen sac but sometimes they appear directly on female buds, especially in times of stress. They are capable of pollinating the female flowers and producing seeds.
Male plants contain 20 times less THC and CBD than female plants, are typically taller than females, and flower one to three weeks ahead of females. A single male flower can produce 350,000 pollen grains; with hundreds of flowers, each plant can release hundreds of millions of pollen grains into the wind and into female flowers. That’s why most growers remove their male plants as soon as it is possible to sex them. Cutting and leaving male plants in the field will not protect against unwanted fertilization of female flowers. The male flowers must be removed from the field. Fun fact: In the midwestern United States, 36 percent of late-summer pollen comes from wild cannabis! So your hay fever might be an allergy to cannabis, not ragweed.
This male flower is almost ready to open and release pollen.
Male plants are typically taller than females and contain 20 times less THC and CBD. Identifying a male plant early on is crucial to prevent unwanted pollination.
The plants’ preflowers will indicate their sex during the vegetative phase. Female preflowers show two little white hairs, the pistils. Male preflowers show a small bulbous ball and no hairs.
This is a very early male flower. If you can identify at this stage, you can decrease the risk of pollinating any female plants in the area.
The ability to identify a male plant early on is crucial to prevent unwanted pollination. Tests exist that can sex a plant by the leaf as early as a few weeks after germination. In states that regulate how many plants you can legally grow, it might be worth the money to test your plants early on to identify and remove males from the garden. If you don’t want to pay for testing, there are guidelines that are useful in identifying male plants. First, if your plants are all of one cultivar, keep an eye out for the taller ones; they may be males. This is not a definitive indication of sex, just an early indicator. Second, the plants’ preflowers will indicate their sex during the vegetative phase. Look for preflowers at the junction of the leaves and the main stem; they will appear approximately 10 weeks after germination. Female preflowers show two little white hairs, the pistils. Male preflowers show a small bulbous ball and no hairs. It can be difficult to spot the ball, but the presence of the two hairs signals a female.
Cannabis is typically grown as an annual, completing its life cycle in less than a year. A seed planted in the spring will grow into a tall plant through the summer and flower in the fall, producing more seeds to start the cycle again the following spring.
Life begins for the cannabis plant when the seed germinates, which takes 3 to 10 days after planting. One surefire way to germinate seeds is to sandwich them between layers of wet but wrung-out paper towels, seal it all inside a Ziploc bag, and store in a warm place. If you’re starting hundreds of plants, it is probably best to sow directly into warm, moist soil that gets at least 16 to 18 hours of light. Seedlings should be protected from frost; if you live in the northeastern United States, start your plants indoors with supplemental light or wait until the danger of frost has passed. After germination, the tiny seedlings begin to grow rootlets branching out from the single root, and true leaves begin to form and grow.
In the fall, female plants grow flowers sticky with resin in the hopes of catching male pollen carried by the wind. Fertilized female flowers put energy into producing seeds to continue the life cycle.
During the warm summer months, cannabis plants can grow a few inches in a day!
Vegetative growth can be astounding! On a hot summer day you can see growth of a few inches a day. The cannabis plant spends most of its vegetative growth phase accumulating bulk in its roots and stems and leafing out. Vegetative growth is triggered when the plant receives more than 12 hours of daylight per day. When the day length decreases to less than 12 hours, the plant transitions from vegetative growth to full-scale flower production. Where I live in upstate New York, outdoor plants begin their real growth spurt in June and, depending on the variety, begin flowering in August or early September.
After the long days of summer, when days shorten to less than 12 hours, the cannabis plant heads into its final life cycle and begins its work in perpetuating the species. In autumn, female plants continue to grow flowers sticky with resin in the hopes of catching male pollen (sperm) carried by the wind. Fertilized female flowers put energy into producing seeds, which, after fully developing, drop to the ground to become next year’s expression.
The length of each cultivar’s flowering period is genetically predetermined, but all are roughly between 45 and 90 days. People living in northern latitudes should avoid cultivars with long flowering periods because frost can set in before flowering is complete. Reputable seed companies will provide this information (see the Resources section).
At some point during flowering, trichome color changes from clear to cloudy to golden as the plant matures. To see this change, you’ll need a hand lens of at least 10× power. The optimum time to harvest is when the trichomes are mostly cloudy and beginning to turn golden; this is when they are the most packed with cannabinoids and terpenes. Clear trichomes are not fully matured, and medicine made from the plant at this stage can leave a person feeling jittery. Medicine made from a plant with trichomes that are fully golden, on the other hand, will often have more sedative effects.
Cannabis, like all plants, has hundreds (possibly thousands) of chemical constituents. Think of plant constituents as instruments playing in an orchestra; when they’re all playing together, they can create a beautiful symphony. While it is interesting to understand what each instrument contributes on its own, the full power of the symphony is revealed only when the entire orchestra works together as one. Similarly, as we single out the constituents of cannabis here and discuss how each functions in the body, we must remember that they also work in coordination with one another within the plant and our body.
We use the many gifts of cannabis and her wisdom when we make medicine. We can broadly divide the more than 500 identified chemical constituents into four categories: acids, cannabinoids, terpenes, and flavonoids. We will spend most of our discussion on cannabinoids and terpenes because most of the research has been done with them.
Cannabis communicates with us and brings about physical healing when her chemical constituents bind with the receptors of our endocannabinoid system. Understanding the chemistry of cannabis will help us understand how she interacts with our chemistry, which will ultimately enable us to make better medicine.
Acids: THCA, CBDA, CBCA, THCVA, CBGA. These acid forms of cannabinoids are precursors to the active forms (created when the acid is removed through decarboxylation). Many have healing properties themselves.
Cannabinoids: THC, CBD, CBG, CBC, CBDV, THCV, CBN. These are the active forms of the above acids, the main constituents used in healing.
Terpenes: beta-myrcene, beta-caryophyllene, d-limonene, linalool, pulegone, eucalyptol, alpha-pinene, alpha-terpineol, terpineol, and many more! Terpenes are chemical compounds with repeating sequences of carbon and hydrogen. We recognize them in cannabis by their smell.
Flavonoids: apigenin, quercetin, cannaflavin-A, beta-sitosterol, luteolin, lutein, xanthophylls. Flavonoids are water-soluble pigments ranging in color from yellow to red to blue-purple. They are powerful antioxidants and anti-inflammatories.
Cannabinoids are the active constituents of the cannabis plant with the acid removed; they have beneficial healing functions in the body.
THC was first isolated in 1964, prompting a search for the receptors that it binds to. The first receptor, named cannabinoid 1 (CB1), was discovered in 1988. In 1992, we discovered that our bodies manufacture a molecule similar to THC, which in turn led to the discovery of the endocannabinoid system, a system we continue to learn about.
THC acts as an insecticide and fungicide for the cannabis plant. When it is released from the glands it also causes necrosis of the leaves around the flower at senescence (biological aging), which increases fertility of the female flowers by exposing more of their voluptuous stickiness to the wind and airborne pollen. THC levels increase with more light.
THC is highly lipophilic (lipid loving), so once absorbed, it travels in the blood bound to lipoproteins and albumin. It can either diffuse out of the bloodstream to interact with various target tissues and receptors (having effects on the body) or travel through the blood and enter the liver for detoxification. The liver detoxifies substances for excretion using a variety of enzymes, the most well-known of which are the cytochrome P450 enzymes (CYP450). THC is also stored in adipose (fat) tissue. It has a half-life of one to three days in blood.
THC has myriad functions in the body: it is an analgesic, anticonvulsant, antiemetic, anti-inflammatory, antinociceptive, antioxidant, antispasmodic, anxiogenic, and anxiolytic. It decreases angiogenesis, metastasis, and tumor growth. It’s a euphoric, intoxicant, muscle relaxant, and neuroprotector. It induces apoptosis, potentiates chemotherapy meds, enhances opioid receptors, and is a sedative.
THC mimics endocannabinoids — our endogenous chemicals — and binds to our endocannabinoid receptors. Once there, it can modulate and regulate the immune system, ease inflammation and pain, and induce apoptosis (programmed cell death). It can help us relax and sleep. It can affect our cognition, emotional memory, and learning. It can ease nausea and cause hunger. When we understand how our own system functions, we can better understand how plant medicine works.
THC plays a role in every body system, including the immune system and the digestive system. When we ingest THC from the cannabis plant, it mimics our own internal cannabinoids (AEA and 2AG).
THC and the Central Nervous System
At the level of the central nervous system (the brain and spinal cord), THC is energetic, euphoric, and intoxicating, causing spatial and temporal perception disorientation, motor discoordination, and short-term memory loss. It is psychoactive and a sedative. At higher concentrations and unopposed by CBD, THC increases anxiety (interestingly, it can also decrease anxiety, a paradox we’ll discuss later).
THC and the Immune System
The immune system defends the body against foreign invaders (and against your own cells when they go rogue). It surveys the body for injury and signals for help. The immune system itself can be thought of as an intelligent system of communication: imagine tiny brains floating through all parts of your body. THC functions in the immune system to decrease inflammation and help protect the body against its own cells if they go rogue by inducing cancer-cell death, decreasing cancer-cell migration (metastasis), and throttling the growth of blood vessels to tumors (angiogenesis).
Because of its intoxicating properties, THC pharmacokinetics (the way a drug moves through the body) and pharmacodynamics (how a drug interacts with living structures) have been heavily studied; the nonintoxicating constituents of cannabis, with the exception of CBD, have not received nearly as much attention. CBD, because of its potent applications for healing (and its moneymaking potential for drug companies), is also now being heavily researched. The more studies we do, the more information we will have to make good decisions about medicine.
THC most often reaches the bloodstream through inhalation or oral ingestion, but it can also be absorbed rectally and sublingually through blood vessels under the tongue. THC has limited transdermal absorption through the skin for entering the bloodstream but can act locally at the site of application.
When THC enters the bloodstream through the lungs, it travels first to the heart and then throughout the body, causing effects within 10 minutes. Only between 2 and 56 percent of inhaled THC makes it into the bloodstream (depending on the experience of the user and how much they are able to inhale), and a portion of that is broken down by the liver. Compared to other psychotropic drugs, THC is relatively slow-acting because its interaction with the body is rather complex. In general, the effects of inhaled THC in the brain are more delayed in onset than other inhaled psychotropic agents because the effects of THC are mediated further downstream than its primary binding site on the cannabinoid receptor.
When we consume cannabis as an edible or tincture, THC enters the bloodstream through the gut lining. It then travels to the liver, where a portion is transformed — presto chango! — into the metabolite 11-hydroxy-THC, which is 5 to 10 times more potent than plain THC. Some 11-hydroxy-THC is broken down immediately, but if you’ve ingested more than the liver can quickly eliminate, or if the liver is busy processing something else, some 11-hydroxy-THC gets into the bloodstream, where it will travel around like inhaled THC and produce the same body effects. Since 11-hydroxy-THC is more powerful than inhaled THC, edibles can be quite potent!
Although edibles may be more potent, the effects take longer to appear, anywhere from 45 minutes to 3 hours, depending the contents of the stomach and how full it is, how well absorption occurs, and liver health. Tinctures are absorbed in 15 to 30 minutes, with the same mitigating factors as edibles. Peak concentration in the blood occurs in 1 to 8 hours. Bioavailability of orally ingested THC is 6 to 20 percent.
There is lot of hype around sublingual/buccal sprays (see below), but the evidence shows that they are pretty much comparable to tinctures in absorption. Sublingual absorption seems to have less variability, with bioavailability around 6 percent, and after initial absorption in the mouth there is no first-pass metabolism at the liver for removal from circulation.
Bioavailability of THC via the rectum is two times higher than the oral route because of increased absorption rate and a decreased first-pass metabolism by the liver. It takes 2 to 8 hours for peak concentrations to occur in the blood.
Absorption of THC through the skin into the bloodstream is close to zero due to the lipophilicity of cannabinoids — they tend to accumulate in the skin without passing into the blood. Topical use of THC is beneficial, however, for localized applications.
Although the brain, small intestine, and lungs can all break down THC, the liver does most of the work. The liver breaks THC down into approximately 100 metabolites, but the majority is 11-hydroxy-THC, which is 5 to 10 times more psychoactive than THC because it so easily crosses the blood-brain barrier. “First-pass metabolism” is when THC is broken down by the liver before it can circulate and produce effects. Because anything absorbed by the intestines is first sent by the blood to the liver, orally administrated cannabinoids have less bioavailability than inhaled cannabinoids. The second phase of liver detoxification of THC results in the production of 11-nor-9-carboxy-THC or THC-COOH, which are both water soluble, not active in the body, and ready for the kidney to excrete.
The liver breaks down THC in two phases.
About 80 to 90 percent of THC is excreted within five days; 65 percent is excreted in the feces as 11-OH-THC, and 20 percent is excreted in the urine as 11-nor-9-carboxy-THC or THC-COOH. THC-COOH can be detected in the urine 30 minutes after a single dose of inhaled cannabis.
CBD is a relative newcomer on the cannabinoid scene. It was isolated in 1940 but wasn’t identified until 1963. Because it is not an intoxicant or euphoriant, high-CBD plants have never been historically selected for the way high-THC plants have been. Nevertheless, CBD and THC are found in equal concentrations in Cannabis indica afghanica (BLD), likely because the selection pressures for making hashish favored plants with high resin content, and resin is rich in CBD. CBD is also the dominant cannabinoid in Cannabis sativa (NLH).
Cannabidiol protects the plant from ultraviolet (UV) radiation and acts as an animal and insect deterrent.
The ability of CBD to bind to a vast array of targets underlies the myriad beneficial effects it has on the body. CBD’s ability to bind to, or affect the binding properties of, different receptors is fundamental to its healing benefits.
In general, CBD modulates the endocannabinoid system. It is analgesic, antiemetic, anti-inflammatory, antioxidant, antipsychotic, and anxiolytic. It modulates the immune system and the effects of THC. It is neurogenic, neuroprotective, nonintoxicating, procognitive, psychoactive, and promotes neurite outgrowth and synaptic growth.
Now some specifics to amaze you . . .
Modulation of the Endocannabinoid System
CBD modulates the endocannabinoid system in two ways. First, it inhibits the reuptake of our own endocannabinoid, arachidonoyl ethanolamide (AEA), at the fatty acid–binding protein (FABP) transporter, thus keeping AEA circulating and active in the blood for longer. Second, CBD inhibits the enzyme FAAH, which breaks down AEA. Both mechanisms increase AEA levels and keep AEA in circulation longer, which is why some people experience mood elevation when they start consuming CBD-rich cannabis.
Modulation of the Effects of THC
CBD has a low affinity for cannabinoid (CB) receptors. It actually doesn’t bind to the active site of a cannabinoid receptor (which are cell membrane receptors found throughout the body that are part of the endocannabinoid system). At very low concentrations, CBD actually acts opposite to what we would expect from an agonist molecule binding to a CB receptor. The action of CBD weakly binding to the CB receptor displaces some THC from binding and modulates the effects of THC, such as sedation, anxiety, and tachycardia. CBD weakly binding to the CB receptor also prevents some of the potent form of THC (that is, 11-hydroxy-THC) from binding to the receptor. The net effect is that less THC binds to CB1 and CB2 receptors, which has been shown to decrease psychosis, increase analgesia, increase the tolerability of THC, widen THC’s window of activity, increase the volume of the hippocampus and amygdala, and potentiate the reduction of pain and inflammation. These effects were shown in a study of people who were given 200 mg of CBD per day for 10 weeks.
CBD and the Immune System
The effects of CBD on the immune system are nuanced and somewhat unexpected, but they fall into two categories: decreasing inflammation and fighting cancer. Cannabis is not an herb for combating colds, flu, or bacterial infections. Instead it systemically reduces inflammation (especially chronic) and fights cancer cells. CBD also increases production of natural killer cells (NKCs), which fight virus-infected cells and tumors.
CBD suppresses adaptive (learned) immune responses by quieting the activation of microglia (glia cells in the brain and spinal cord), decreasing proliferation and maturation of neutrophils (white blood cells), and inducing apoptosis (death) of monocytes and lymphocytes (other types of white blood cells) in the spleen and thymus. The suppression of the adaptive immune response is not a general suppression but rather an adaptive response to immune cells and microglia, increasing their production of inflammatory cytokines. This is the mechanism for shutting down inflammation. The production of inflammatory cytokines in the absence of an acute trigger is the definition of chronic inflammation; it is maladaptive and a contributing factor in chronic disease.
Identified in 1964, CBG is decarboxylated CBGA, the precursor molecule for THC, CBD, and terpenes. CBG can be found in hemp fiber cultivars and some high-THC cultivars. CBG is still relatively new to the science community, so we have limited information on its benefits. CBG does look promising for fighting oral, prostate, and breast cancer. It may have antidepressant, antiemetic, antifungal, anti-inflammatory, antinausea, antiseptic, and neuroprotective properties. It decreases optic pressure, and increases AEA. CBG might also be a muscle relaxant and may promote skin cell proliferation.
Cannabichromene acid (CBCA) is the acid form of CBC before decarboxylation. It is found in the early flowers of some cannabis cultivars and may protect the plant against fungal and bacterial infections during the flowering phase. CBC is an analgesic, an antidepressant, an anti-inflammatory, a sedative, and a potent inhibitor of AEA reuptake.
CBDV is an analogue of CBD found in feral plant populations in India; most strains don’t contain this constituent. We know that it is analgesic and increases production of 2AG, an endocannabinoid produced by the body. CBDV is currently being tested for its effects on type 2 diabetes, glaucoma, schizophrenia, seizures, and neonatal hypoxia.
THCV is an analogue of THC with enough chemical differences to prevent its usefulness as a euphoriant or intoxicant. It is a minor cannabinoid found in cultivars from South Africa. It is an anticonvulsant, decreases body fat, lowers CB1- and CB2-induced hyperalgesia and inflammation, and at low doses reduces the effects of THC.
CBN is not found in live cannabis plants but is rather an oxidative by-product of THC or CBD, so the older a dried flower, resin, or oil is, the more CBN it will contain. CBN will naturally oxidize from THC and CBD in our medicines or dried flowers after approximately three years. CBN is not an intoxicant or euphoriant. It is anticonvulsant and anti-inflammatory, decreases keratinocyte overproliferation (as seen in psoriasis), and has sedative properties.
CBDA is the acid form of CBD. It is found in live plants and dried flowers that have not been decarboxylated. It is anti-inflammatory, analgesic, and binds the serotonin receptor 100 times more powerfully than CBD. The action at the serotonin receptor may also alleviate nausea and vomiting, anxiety, and depression.
THCA in the plant functions to protect against insect predation. When released, it causes apoptosis in the insect. In the human body, it is an anti-inflammatory, antiemetic, and analgesic.
Terpenes are classified chemically by the presence of repeating chains of carbon and hydrogen atoms (hydrocarbons).
Cannabis has more than 200 identified terpenes. As we identify them and learn more about their effects both in the plant itself and on our bodies, terpenes are becoming an increasingly important part of the constituent profiles being built for each strain of cannabis. Two different cannabis strains (say, an indica and a sativa) with exactly the same cannabinoid profile (for simplicity’s sake, let’s say they have the same THC and CBD ratios and percentages) might have extremely different healing capabilities. The difference comes from their varied terpene profiles.
One of the ways plants, through their terpenes, interact with us is through our sense of smell. Since terpenes are volatile and “smelly”, we can interact with the plant. Olfaction, or our sense of smell, is processed in the oldest part of our brain and connects us to memories, to poison, to spoiled food, and lastly with spirit. The light terpene molecules released from the trichomes travel through the air into our nose and bind to olfactory receptors at the top of our nasal cavity. That activates a nerve impulse (electric current) that travels to the olfactory area of our brain and registers the scent of what we are smelling (“pine with a hint of lavender”). We understand indefinable things about our world, including plants, through our sense of smell. Plants communicate with each other and us through the olfactory universe of terpenes. We may not have the science to measure it yet, but that doesn’t mean this communication is not happening.
I am an herbalist, not an aromatherapist, and my understanding of essential oils is limited. I do understand a simple yet profound and trustworthy diagnostic: if you like the smell of a plant, you’re on the right track for working with it. If you don’t like the smell, that particular cultivar might not be for you.
You or your client may or may not have access to labs for testing plant profiles. (As we’ve discussed, you can’t always be sure the plant you have in front of you is the plant the person who gave it to you says it is.) You can “test” the plant yourself for basic characteristics, such as whether or not it is energizing, sedating, or anxiolytic, to know the basic criteria of the flowers of your apothecary. A further diagnostic for your clients (or yourself) would be to smell the flowers, holding the intention of what assistance you would like from the plant. The nose knows, and it can’t lie.
Terpenes and sesquiterpenes (heavy, extra-complicated terpenes), like cannabinoids, are made in the trichomes from acetyl CoA, the same precursor molecule of CBD, THC, and cannabigerolic acid. The number and types of terpenes produced in a plant are determined by genetics; terpene concentration also increases with sunlight and decreases with soil fertility. Plants make terpenes in part for protection against predation: produced by trichomes at the tops of the plants, bitter terpenes act as antifeedants against foragers. Terpenes and sesquiterpenes are also sticky and so can trap marauding insects before they cause too much damage. Finally, some terpenes offer protection against bacterial and fungal infections.
Some terpenes can bind to the CB2, GABA, NMDA, adenosine A2A, or 5-HT receptors. Like all essential oils, terpenes also bind to olfactory receptors in the nose. Terpenes are pharmacologically versatile. They can interact with receptors at the cell membrane or with ion channels within a muscle cell or neuron. They are able to change the fluidity of certain membranes, altering the permeability of the blood-brain barrier and the skin barrier. This change in membrane fluidity can increase the affinity of THC for the CB1 receptor and increase THC absorption across the blood-brain barrier, which could affect THC’s analgesic and mood-altering properties.
The monoterpenes beta-myrcene, limonene, and pinene are all insect repellents and found in highest concentrations at the top of the cannabis plant. We will discuss a few, but not all, of the terpenes here.
Beta-myrcene is the most abundant terpene in fresh cannabis; it is also found in hops and mango. It is analgesic, anti-inflammatory, antimutagenic, antiproliferative, and antipsychotic, and it increases the effects of THC in the brain. Cultivars with higher than 0.5 percent beta-myrcene tend to be sedating, whereas cultivars with less than 0.5 percent tend to be energizing.
Limonene is the second most abundant terpene in fresh cannabis; it is also found in high amounts in citrus fruits. It is antibacterial, anticonvulsant, antidepressant, antifungal, and anxiolytic, and it decreases gastroesophageal reflux and serum cortisol (helping with stress). It is an immunostimulant and induces apoptosis in breast cancer cells.
Pinene is the most abundant terpene in the plant world. It acts as a bronchodilator, increasing the absorption of other constituents when inhaled. It also is antibiotic, is anti-inflammatory, promotes focus and memory, and increases energy and sense of self-satisfaction. Cultivars with high amounts of pinene would be helpful for focus and concentration.
Linalool is responsible for the floral scent of lavender. It is an analgesic; has anticancer, anticonvulsant, antipsychotic, and anxiolytic properties; can be used as a local anesthetic or sedative; and supports sleep.
Terpinolene is found in lilac, apple, cumin, tea tree, lemon, sage, marjoram, rosemary, and pine. Some strains can be as much as 53 percent terpinolene. It has antibacterial, anticancer, antifungal, and antioxidant properties and is a sedative.
Sesquiterpenes are heavier molecules. They are less volatile than terpenes and have stronger odors. They are also anti-inflammatory and have bactericidal properties.
Caryophyllene is the most abundant sesquiterpene in the dried cannabis flower. It has a sweet and woody smell and is also found in black pepper, cinnamon, and clove. It is highly lipophilic, meaning it crosses the blood-brain barrier easily and is highly available to the brain. It also acts as an analgesic, anti-addictive, antibacterial, antidepressant, anti-inflammatory, antioxidant, antiproliferative, antiseizure, antispasmodic, and anxiolytic.
Humulene is found in clove, basil, and hops. It carries a subtle earthy, woody aroma with spicy herbal notes. It is analgesic, antibacterial, anti-inflammatory, and antitumor, and it decreases appetite.
Flavonoids are commonly known as plant pigments and protect the plants from damaging ultraviolet radiation. The pigments in other flowers (cannabis is wind pollinated) also attract pollinating birds and insects, carrying on the dance of reproduction. Do you like the purple color of your “blueberry muffin” cannabis strain? You can thank the flavonoids anthoxanthin and anthocyanin. Flavonoids are lost upon heating, so fresh preparations are necessary to retain the benefits of flavonoids in medicine. Try juicing, tinctures, or unheated oils.
Cannabis makes approximately 20 flavonoids, including apigenin, beta-sitosterol, cannaflavin (unique to cannabis), kaempferol, lutein, luteolin, orientin, quercetin, silymarin (also found in milk thistle), vitexin, and xanthophylls — all with anti-inflammatory, antifungal, antiviral, antioxidant, and anticancer potential. We use flavonoids as antioxidants and anti-inflammatory agents and to help prevent diseases associated with chronic inflammation. Cannaflavin A has anti-inflammatory properties and is 30 times more effective than aspirin at decreasing the inflammatory prostaglandin PGE2.
Chlorophyll, another pigment, gives plants their vibrant green color just like hemoglobin gives our blood its rich red color. The two molecules are almost exactly identical except for the element the molecule is built around. Hemoglobin is built around iron, while chlorophyll is built around magnesium. The gorgeous color in your infused oils and tinctures and teas comes from the extracted chlorophyll from the plant into your tea. Chlorophyll aids in the production of our red blood cells; it is anti-inflammatory, antioxidant, and antimutagenic, and it protects us from carcinogens.