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How does cannabis get you high?

How do marijuana’s psychoactive properties work?

Have you ever looked at your hands? I mean really looked at your hands?

You might think you have, but as the above classic Doonesbury cartoon implies, people who are high on cannabis may perceive mundane objects to be far more fascinating than usual.

How is it that a plant that first emerged on what’s now the Tibetan Plateau can change humans’ perception of reality? The secret lies in a class of compounds called cannabinoids. While cannabis plants are known to produce at least 140 types of cannabinoids, there’s one that’s largely responsible for many of the effects of feeling high. It’s called tetrahydrocannabinol, or THC.

When a person smokes or inhales cannabis, THC “goes into your lungs and gets absorbed … into the blood,” according to Daniele Piomelli, a professor of anatomy & neurobiology, biological chemistry, and pharmacology at the University of California, Irvine School of Medicine. Edibles take slightly longer trip through the liver, where enzymes transform THC into a different compound that takes a bit longer to have an effect on people’s perception of reality.

THC that’s inhaled “reaches pretty high levels fairly quickly,” Piomelli told Live Science. Within 20 minutes, the circulatory system is carrying molecules of THC to every tissue in the body, including the brain, where it can alter neural chemistry.

“From the lungs, it’s a pretty straight shot to the brain,” according to Kelly Drew, a professor of chemistry and biochemistry at the University of Alaska Fairbanks.

The THC molecules that pass the blood-brain barrier will find that they fit snugly into receptors that ordinarily receive compounds called endocannabinoids, which the body produces itself. These receptors are part of the endocannabinoid system, which is involved in several functions, including stress, food intake, metabolism and pain, according to Piomelli, who also directs the Center for the Study of Cannabis at UC Irvine.

“The endocannabinoid system is the most pervasive, diffused and important modulatory system in the brain because it controls the release of pretty much every neurotransmitter,” Piomelli said. Neurotransmitters are molecules that brain cells, or neurons, use to communicate with each other. One neuron sends a message to the next by releasing neurotransmitters, such as dopamine or serotonin, into an infinitesimal gap that separates one neuron from the next. The gap is called the synapse.

The neuron on the receiving end of the synapse is called the postsynaptic neuron, and it “decides whether to fire based on the input it receives,” Drew told Live Science. These neural signals cascade through intricate circuits of neural connections that function on a tremendous scale; there are about 85 billion neurons in the brain and as many as 100 trillion connections among them.

The presynaptic neuron sends neurotransmitters across the synapse to the postsynaptic neuron, Piomelli said. But the presynaptic neuron can also receive information. When a postsynaptic neuron has fired, it can send a message across the synapse that says, “the neuron I come from has been activated,” stop sending neurotransmitters, Piomelli said. It sends this “stop” message in the form of endocannabinoids that bind to a receptor called cannabinoid 1 (CB1).

“Like a sledgehammer”

When THC enters the brain, the molecules diffuse into the synapses where they “activate CB1 receptors,” Drew said. THC doesn’t cause the most extreme possible response like some synthetic cannabinoids such as K2 or spice, but it does “turn up the volume” and increase the likelihood that the presynaptic neuron it affects will temporarily stop sending neurotransmitters, she said.

“The high is a very simple phenomenon, Piomelli said. “THC comes in like a sledgehammer,” flooding the endocannabinoid system with signals the postsynaptic neurons didn’t send. When presynaptic neurons across the brain get the memo to stop sending neurotransmitters, this alters the normal flow of information among neurons and results in a high.

Scientists have yet to decipher exactly what happens during this euphoria, however.

That’s because, in part, U.S. legal restrictions make it difficult to study cannabis. But from what researchers have gathered so far, THC appears to temporarily “unplug” the default mode network. This is the brain network that allows us to daydream and think about the past and future. When our brains are focused on a specific task, we quiet this network to let our executive function take control.

There’s evidence that THC has a significant effect on the network, but researchers aren’t quite sure how it happens. There are cannabinoid receptors all over the brain, including in “areas that constitute the key nodes of the [default mode network],” Piomelli said. It could be “that THC deactivates the [default mode network] by combining with those receptors,” but it’s also possible that THC quiets the network through an “indirect effect that involves cannabinoid receptors in other brain regions.”

Scientists are still working to find the mechanisms that result in a person feeling high, but there’s some reason to think this effect on the default mode network is a significant piece of the puzzle.

Unplugging the default mode network “takes us into a mental place where the function of the things we experience is less important than the things themselves: our hands are no longer just something we use for touching or grabbing, but something with inner existence and intrinsic value,” Piomelli said. Psychedelics, such as LSD or dried psilocybin-containing mushrooms, do the same thing.

However, people can experience highs differently. “The feeling of becoming fascinated by and ‘connected’ with ordinary things, things we see and use every day, is not universal but does happen, especially when high doses of THC-containing cannabis are used,” Piomelli said.

THC doesn’t just affect the default mode network. It may also, in the short-term, flood the brain with dopamine, the brain’s reward signal, according to a 2017 study in the journal Nature. (Long-term, it may blunt dopamine’s effects, the study found.) That, in part, may explain some of the euphoria associated with a high, and places cannabis in the company of other drugs that people use to feel pleasure.

“Every drug that has rewarding properties affects that system,” Drew said.

Aftereffects

The effects of a high from cannabis that’s smoked or inhaled typically last for a few hours, though it can take edibles almost that long to start affecting users. And while cannabis isn’t the dangerous substance it was made out to be in the 20th century, using it comes with some risk. For one, while cannabis is legal for recreational and medical use in some states, it’s still illegal in many parts of the country.

It’s also important to bear in mind that cannabis is a potent pharmacological substance. Cannabis can cross the placenta, so pregnant people should avoid it. And “heavy use in the teenage years can be problematic,” Piomelli said. For instance, cannabis — and especially synthetic cannabinoids like spice — can exacerbate psychosis. “People who are at risk for that should not smoke it,” Drew said.

Finally, cannabis does affect the ability to drive, particularly in occasional users. Drew cautioned that people should not drive for three hours after smoking.

Eventually, the THC will leave the brain; the profusion of blood that brought THC into the brain will carry it to the liver, where it will be destroyed and expelled in urine.

And you’re not gonna believe this, but your hands — they were the same the whole time.

Originally published on Live Science.

IMHO, drugs which do not easily cause overdose deaths (like THC, LSD etc) should/must be legally treated same as alcohol (which is really just another kind of drug (which do not easily cause overdose deaths))!

IMHO, just like prohibition of alcohol had caused so much crime in the past (& that is why it had been forced to be repealed later), prohibition of other similar drugs causing so much easily preventable crime today!
We need to take lesson from our past.

It gives people relief without vice.

This is precisely why it has been vilified for so long. You cannot have such things. Fun, pleasure and relief without vice?

That is blasphemy of the highest order for the “divinely” inspired. In their distorted concept of “dealing with life”, you have to tough it out. Anything which circumvents such rigors in life is sinful.

It reminds one of the famous counter-culture response: “Reality is for people who cannot deal with drugs.”

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Here’s how cannabis jumbles up typical brain processing.

How Marijuana Can Alter Your Mental State

Steven Gans, MD is board-certified in psychiatry and is an active supervisor, teacher, and mentor at Massachusetts General Hospital.

Many people who are curious about smoking pot, or who have family members or friends who use the drug, wonder, “What does it feel like to be high?” Although the experience is different for everyone (the marijuana high is one of the most unpredictable of all drug intoxication effects), there are certain effects that most users of marijuana feel when they smoke or eat pot.

When people are stoned on marijuana, the experience is strongly affected by factors that have little to do with the drug, and more to do with the sensitivity of the person taking the drug to their surroundings and their feelings about the people they are with. The frame of mind of the person using marijuana and the environment where they use marijuana that influences the effects are known as set and setting.

Altered Sensory Perceptions

Most people experience changes in their sensory perceptions when they are stoned.   While marijuana does not typically produce real hallucinations the way that hallucinogenic drugs like LSD do, people do tend to see the world in a different way when they are high on cannabis than they do normally.

Familiar faces and objects can seem unfamiliar or strange, often in a way that is amusing; colors can appear brighter; aesthetic appreciation can be enhanced: and the mood of the individual can be projected onto everything around them. When surroundings are perceived in a positive way, this can be enjoyable. But it can also happen in a negative way, causing the world to seem grim and harsh.

The sensory perceptions of hearing and taste are often most strongly affected by marijuana. People who have used marijuana will often report a greater appreciation of music and may spend the entire experience listening to music.

Enhancement of the sense of taste can result in a specific type of binge eating called “the munchies,” in which larger amounts of food may be consumed than normal. People who are stoned may also eat foods in odd combinations, such as chocolate with pickles.

Changes in Mood and Mental State

The effects of marijuana on mood vary greatly from one person to another, but generally, emotions are exaggerated in a similar way to the intoxication effects of alcohol.   Situations that normally seem emotionally neutral may appear amusing or ridiculous, or conversely, intimidating and upsetting.

Marijuana users will typically attempt to control the emotional stimulation they are exposed to while stoned, but this is not always possible. Situations involving real or imagined confrontation can be particularly upsetting and can result in intense paranoia in someone under the influence of marijuana.

The effects of marijuana on the ability to relax are rather contradictory. While many who become dependent on marijuana do so for the drug’s initial relaxation effects, the rebound effect typically results in a higher level of anxiety in marijuana users.   Some develop long-term anxiety disorders, which they attempt to self-medicate with marijuana, causing a vicious cycle.

People often feel confused or slowed down when they are high on marijuana, although this is often not upsetting and can even seem amusing to the person affected. Rarely does marijuana improve mental functioning.

Effects on Creativity

While some people claim that marijuana improves creativity, and there is some evidence that marijuana use is associated with the production of a greater number of novel ideas, it is unclear whether people who have novel ideas seek out marijuana, or whether the drug increases the novel ideas.

Also, some research has shown that higher doses result in less creativity than lower doses. One study did not find significant differences in the creativity of individuals using low dose THC and those not under the effects of marijuana at all.  

Typically, people under the influence of marijuana express ideas that may seem bizarre, muddled, unfeasible, or incomprehensible to others. Some would-be artists use marijuana in the hope of a shortcut to artistic success—however, marijuana may make it more difficult to use creative thoughts productively.

The marijuana high can be unpredictable. Although there are effects that users describe that are common to the experience, it's different for all. ]]>