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In my previous post, I described my first experience with marijuana. Now I will explain how marijuana acts on the brain to change the texture of experience.

Exactly how does marijuana get us high? The answer is best approached as a story about marijuana researchers’ discoveries about the brain. Marijuana cannot be understood without understanding the neuroscience underlying its action in the brain.

For years I had no better explanation for how marijuana’s effect than to parrot the impressive chemical name of pot’s major psychoactive component—delta-9-tetrahydrocannabinol —THC, which was isolated and its structure determined by the Israeli researcher Raphael Mechoulam in 1964.

For as much as anyone knew about delta-9-tetrahydrocannabinol, we might as well have called it pixie dust. Devotees often talked of marijuana as though smoking it imbued them with the plant’s numinous spirit. Mysticism fit comfortably with being high during the Age of Aquarius. The Love Drug.

Despite ignorance about how marijuana worked, my career in addiction psychiatry enabled me to talk to many marijuana users. While Peter Kramer was listening to Prozac, I was listening to marijuana.

Many loved the weed, often for very different reasons. Some reacted with fear, while a small number became psychotic, or had their psychosis worsened. Almost everyone felt some paranoia, for understandable reasons, during the repressive war on drugs.

Then, in the mid-1990s, when more powerful hybrids became available in San Francisco, I began hearing of withdrawal symptoms for the first time, despite conventional wisdom that marijuana was not addictive.

While society mostly paid attention to the growing use of marijuana, the trajectory of basic laboratory research on marijuana followed the same blueprint as opiate research had in discovering our endorphin system. First, opiate research identified morphine as the active ingredient in poppy resin. Then morphine was tracked as blood carried it throughout the brain, where it attached to opiate specific receptors. Finally, in 1964 (the year Mechoulam isolated THC) the brain’s natural (endogenous) morphine-like chemicals were discovered and named with the contraction “endorphins.” Opiates only affect the brain because they mimic endorphins and stimulate endorphin receptors.

Similarly, naturally occurring cannabinoid-specific receptors were eventually discovered in 1988 by using a radioactive modification of THC, the active ingredient in cannabis resin. Called CB1 receptors to distinguish them from similar cannabinoid receptors found throughout the body, they are the most abundant receptor in the brain. Then CB1 receptors were mapped throughout the brain in 1990 and found to be concentrated in specific areas. These areas give rise to mental functions that correspond to characteristics altered by marijuana, i.e., memory, emotion, hunger, etc. Two years later, Raphael Mechoulam’s research team, still at the forefront of cannabinoid research, isolated the naturally occurring (endogenous) THC-like chemical for which CB1 receptors were designed. The first of many endocannabinoids to be discovered was fancifully named anandamide—Sanskrit for bliss. Marijuana only affects the brain because THC mimics endocannabinoids and stimulates receptors specifically designed for responding to endocannabinoid transmitter molecules.

While blood carries THC throughout the brain, it gravitates wherever cannabinoid receptors are most densely packed. When THC’s mimicry of anandamide stimulates the cannabinoid receptors beyond their normal level of activity in a motor area (e.g., the basal ganglia), the resulting excess receptor activity reduces spontaneous motor activity. With a high enough level of THC, an animal is immobilized, though not paralyzed. Sufficiently strong prodding can elicit movement. The technical term for this among marijuana aficionados is “couchlock.” The night described in the previous post, when I lay immobilized on the floor, illustrates couchlock. This motor quiescence adds to the calming effect many feel when high.

A similar pattern is repeated in areas of the brain with high levels of cannabinoid receptors. The hippocampus, where learning and memory begin, is densely populated by receptors. THC’s impact on these hippocampal receptors creates experienced problems with short-term memory. Confusion and laughter often accompany nonsequiturs and sentences that lose track of the subject before getting to the predicate.

Concentrations of receptors in the amygdala, near the front of the temporal lobes, generally calms anxiety when stimulated by THC (though a few individuals have a paradoxical panic reaction). Adding CBD, another chemical in cannabis, along with THC modifies THC’s impact, and the complex role of CBD will be covered in a future post. THC’s stimulation of the amygdala also produces a sense of novelty and wonder, awe or amazement. This sense that the world is being seen new and differently contributes greatly to the pleasure many feel when high.

And, of course, there are the “munchies.” Cannabinoid receptors in the hypothalamus, where experiences of hunger and satiety arise, are strongly activated by THC. In my first experience with marijuana I was quickly mobilized from couchlock by the offer of freshly baked brownies.

On the other hand, the visual area at the back of the brain has the least number of receptors found in the cortex. As a result, vision is relatively unaffected (except for some impact on the pressure within the eye itself).

The bottom line: THC over-activates the endogenous cannabinoid system (ECS) to do more of what it is designed to do. THC dials the ECS up to higher than normal levels of activity, like turning wattage on a light bulb above its normal level. Suddenly, new brightness, and even heat, illuminate everything. Your eye notices new details.

THC only makes the brain do more of what it normally does. There is nothing magic in the plant. Nothing mystical passes from weed into our experience.

But this is still only a small portion of the fascinating story science tells us about marijuana and the brain. Future posts will describe how the normal function of our endogenous cannabinoid system is to regulate the rest of brain chemistry, THC’s impact on our reward center, and how too frequent exposure can cause subtle but measurable lingering effects.

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