The Plant Side: Cannabinoids
Marijuana is composed of over 400 compounds, including about 60 cannabinoids, which are a class of molecules unique to the cannabis plant.Cannabinoids were first identified in the 1940s, but it was not until 1964 that Dr. Raphael Mechoulam of the Hebrew University of Jerusalem isolated delta-9 tetrahydrocannabinol (THC), as the primary psychoactive ingredient in pot, the chemical that gets people high.
THC’s effects are domulated by the other cannabinoids. Along with THC, the main cannabinoids are cannabidiol (CBD), cannabinol (CBN) and cannabigerol (CBG). More than 50 other cannabinoids are either slight chemical variations on these main 4 molecules, or are only present in either small quantities in comparison. THC is by far the most understood.
Cannabinoids are concentrated in the thick resin produced in gladural structures known as trichomes. This name comes from the Greek, and means “growth of hair”. On marijuana plants, trichomes are the tiny stalks with cannabinoid-filled heads that stick up off the buds, leaves and stems. In addition to cannabinoids, trichomes are also rich in terpenes, the chemicals that produce the powerful, distinctive odors of the cannabis plant.
The Human Side: Cannabinoid Receptors
Cannabinoid receptors are found in very large quantities in many different parts of the nervous system, which includes the brain, spinal cord, and the nerves that carry signals between the brain and body. Most of the cannabis high is the result of THC interacting with the cannabinoid receptors in the nervous system.
In 1988 an American research team discovered the part of the brain that picks up THC and other cannabinoids. Dubbed CB-1 receptors, they seem to be responsible for the euphoric and anticonvulsive effects of cannabis. CB-1 receptors are found in many parts of the nervous system and reproductive system, but are virtually absent from areas that control the lungs and heart. Marijuana bypasses these symptoms, making it essentially non-toxic. Most drugs, even aspirin or coffee, act on these vital systems, which means at high enough doses, they can be toxic or fatal to humans. On the contrary, there are no recorded deaths from a marijuana overdose. The effects of THC overconsumption are generally restricted to conditions that may may include severe temporary memory impairment, paranoia and panic, but most often result in sleepiness followed by deep and sometimes prolonged sleep.
Scientists identified a second group of cannabis receptors known as CB-2 receptors. These are found in the immune system, primarily the spleen, but also in other organs. They appear to be responsible for the anti-inflamatory and stress reduction effects of marijuana. The CB-2 receptors may hold the key to many other therapeutic effects that this plant offers, such as immune modulation and tumor reduction.
Having identified these receptors, researchers naturally wondered what they were doing there in the first place. In 1992, Dr. Devane, along with a scientific team working at Dr. Mechoulam’s project, was able to identify the chemical produced by the body naturally that the receptors are there to receive.
Devane named these naturally occuring chemicals “anandamides” after the Sanskrit word for bliss (ananda). Technically, they are described as “endogenous ligands”. They activate the cannabinoid receptors. The effects of the natural chemicals are similar to THCm but act less powerfully and disappear far faster.
The discovery of these anadamides makes it clear that while cannabinoid receptors sure come in handy for getting high on pot, their sole purpose is not to allow humans to get high from cannabis. The cannabinoid system appears to be very ancient, and exists in nearly all species of animals so far investigated – mammals, reptiles and birds, even very simple ones like the microscopic hydra.
According to Mechoulam’s ongoing research, anandamides may play a critical role in controlling many of the body’s biochemical systems, including reproduction, sleep, fight-or-flight and appetite cycles. The presence of these naturally occuring “anadamides” gives new meaning to the saying “get high on life”. Our bodies naturally take advantage of this feel-good chemistry for their own regulatory purposes.
Cannabis – Human Interaction
Once THC reaches a cell, it binds to the receptor, causing changes in the cell’s function, which ultimately result in the physiological or psychological effects of the drug – in other words, it makes you high.
The body absorbs pot when the cannabinoids are released and inhaled as smoke or vapor. They pass thru the lining of the lungs and enter the bloodstream. Blood circulates through the heart, then heads straight for the brain and on to other parts of the body, resulting in a rapid onset of effect.
When cannabis is eaten or drunk as a beverage, the cannabinoids are not absorbed until they’ve made it past the stomach to the intestines, where they’re absorbed into the blood, which passes through the liver before distribution to the brain and other parts of the body.
Once THC passes through the liver, it is chemically modified into 11-hydroxy-THC. Because digestion and absorption are relatively inefficient and slow, the effects are delayed for 30-60 minutes from consumption, but once they begin, they last longer.
The quality of the “high” from inhalation versus eating may be different, since most of the eaten THC will be modified by the liver. Also, only about 30% of the THC is absorbed when eaten, while 50-75% is absorbed when pot is inhaled, whether smoked or vaporized.
A scientific study of subjects smoking marijuana determined what factors affected blood levels of THC. It was discovered that longer breath holding time was more important than the number of puffs taken of the “puff volume”. That’s right. Roll your eyes at your smoking pals when they seem on the verge of exploding from holding an inhale – science is on their side.
Once pot reaches the receptors, it has a multitude of effect. Scientific researchers have indicated four main groups of psychological categories that make up the high:
Emotional – euphoria, easy laughter, decreased anxiety.
Sensory – increased or altered perception of external stimuli; increased awareness of one’s own body.
Somatic – feeling of floating or sinking, impaired balance.
Cognitive – distortion of time perception, memory lapses, difficulty concentrating.
Physiological effects may include a brief increase in heart rate and blood pressure, red eyes, dry mouth, decreased activity of the intestines and decreased nausea, analgesia (pain relief), decreased convulsions (anti-seizure) and decreased muscle spasms. These effects may be present to greater or lesser degrees depending on the balance of cannabinoids and the amount of the dose.
The Science of Variety
Remember the two types of receptors? THC attaches primarily to CB-1 receptors, while CBD has an affinity for CB-2 receptors. Since some varieties have a larger proportion of CBD relative to THC or vice versa, this is one scientific basis for different producing a range of effects. More CBD typically produces a heavier, “body high”, helpful with sleep or inflammation. More THC typically affects the head more, generating euphoria and energy.
Connosseurs appreciate the subtleties of variation in the highs marijuana can impart. Now, the medical community is just beginning to identify physiologic reactions to certain strains that may benefit specific conditions. So far, it is believed that THC mediates pain and provides neuroprotection, while CBD relieve convulsion, inflammation, anxiety, and nausea.
GW Pharmaceuticals, the British firm, has spent years and millions of dollars researching and developing cannabis-based medications. They have found that particular balances of these two cannabinoids produce measurably different effects in patients. For instance, THC or CBD alone do not help pain management nearly as much as an equal balance between two.
Other cannabinoids also appear to have profound effects on physical function and health. Since 2002, cancer researchers have identified cannabinoids responsible for tumor reduction, triggering the natural cell death that keeps tumors from growing and cutting off the blood supply to tumors that have already developed.
Identifying and developing strains of marijuana that contain particular ratios of cannabinoids and other chemicals should prove to be some of the most important work of the next decade.