 No topic seems to rile the internet up like talking about cannabis. All the elements of a perfect storm are here, highly biased advocates on either side, a lot of misinformation, and an open forum to discuss it. What has been missing, I think, is an accurate look at what science can support about the effects of cannabis and how it works. What I propose to do in a short series of videos is to dig a little deeper into the biology behind cannabis and cannabinoids. I'll be using primary peer-reviewed literature throughout, sources in the description. First we need to understand the different classes of cannabinoids. Your body manufactures endocannabinoids, and these have abbreviated names like 2AG, AEA, and NADA. These substances are made by your cells to regulate the way your various systems work. In order for these signals to do anything, they have to be received. And for that we need a receptor protein on the surface of a cell. A cannabinoid receptor is a very specialized tool that detects one of these endocannabinoids and passes the signal to the cell to respond appropriately. You can think of these receptors as equivalent to a light switch and a circuit diagram. Your body has two types of receptors specialized for endocannabinoids. We call them CB1 and CB2. CB1 is on the surface of nerve cells in the brain, and we'll talk about that shortly. CB2, though, is found mostly on white blood cells, but also in the heart, lung, and blood vessels. In the brain, when the light switch that is CB1 is flipped on by endocannabinoids, it modulates the way that nerve responds to other signals. Here's a key point about cannabinoid receptors. They are a class of receptors called G-protein coupled receptors, or GPCRs. If we're going to stick with our light switch analogy, they don't directly turn the lights off or on. Instead, they change the way other light switches on the same circuit work, reversing the normal on-off response, or dampening or amplifying the response through a long chain of events. They're modifiers of other responses, rather than being direct signals themselves. We'll talk later about the consequences of that. In the brain, endocannabinoids, binding to CB1 receptors, change the way our brains store memories, set our mood, tell us we're hungry and sense pain. However, the second receptor, CB2, uses different endocannabinoids to change the way our immune systems work, including making cells self-destruct or produce damaging free radicals. They can also change the tightness of our blood vessels and how we respond to bacterial infections or other invaders. We've talked so far about endocannabinoids, the ones our bodies produce. One of the other classes are the phytocannabinoids, the cannabinoids found in plants, or more specifically in cannabis. THC and CBD are phytocannabinoids, and combine their represent the two most abundant substances found in POT. These substances, when ingested, interact with our cannabinoid receptors more strongly, regardless of whether they are smoking or eaten or vaporized. The action of phytocannabinoids is to alter dramatically the balance of the endocannabinoid system. That's why they're used by recreational users. They interfere with normal mood regulation, normal pain sensation. They put the user in an altered state by overwhelming normal function. Our light switch is in a super on, can't be turned off state that lasts as long as the high. THC binds the CB1 receptor, which gives the psychological high, altering the way the brain functions. But it also binds CB2 receptor, which means that it changes the immune system and affects the lungs, heart, and blood vessels. The other major cannabinoid found in POT is CBD, which blocks the receptors without producing a signal to the cell. That means it's an antagonist. It opposes the actions of agonists like THC. It also has no detectable psychoactive effects. The mixture of agonist and antagonist, the nature of cannabinoid signaling as a modifier of other signals, means that the health effects of cannabis are hard to study, somewhat unpredictable, paradoxical from one situation to the next. Cannabis for example in nerve cells is both neurotoxic and neuroprotective. It increases anxiety and also lowers it. It reduces vomiting and nausea, or it can drive it to a new high called hyper-amesis. It can kill cancer cells or trigger them to become more resistant. It causes changes in the brain that mirror schizophrenia, yet in patients with schizophrenia it can help to manage their symptoms. It's a bronchodilator and also can trigger asthma. It relaxes blood vessels and also makes them constrict. This is not a good profile for a therapeutic drug, and I would argue not a good profile for a recreational drug either. It's a bit of a nightmare for a researcher trying to make sense of things. This is why I'm skeptical of any unqualified claims of health benefits. What phytocannabinoids do in a highly simplified setup, say neurons growing in a flask or human tumor cells injected into mice, will likely not be replicated in a large population of people. Some will be treated effectively, others might possibly be worsened. So far we've talked about endocannabinoids, the signaling lipids our bodies use to regulate normal functioning. We've talked about phytocannabinoids, the plant-based substances with high activity and low specificity that often have contradictory, unpredictable effects. The last class of cannabinoids are the synthetics. The most interesting of these combine high activity and high specificity. They have names like JWH 018, HU 210, AM 2201. They're made by chemists in labs and have been since the 1960s. I personally have high hopes that at least a few of these are going to end up as actual effective therapeutic drugs. The final product will likely not be psychoactive on purpose so that people don't use it to get high and end up damaging their brains or other organs as a result. Unfortunately we've already seen what happens to JWH 018, which is a major component in K2 or SPICE when it hits the streets. It's accounted for a few dozen deaths from cannabinoid overdose and the abuse potential is very high. These substances have high activity but lower specificity than most of the synthetics, mostly because they're based so closely on the plant equivalents. In a few years though, I suspect we will see the emergence of better cannabinoid drugs. They're not going to be miracle cures for anything, but they will complement other effective therapies and broaden our arsenal and that's something I fully support. In part two I'll talk about some of the long term consequences of using cannabis on your physiology and we'll address the old myth that no one has ever died from cannabis. Thanks for watching.