What Is Cannabis Doing to Our Brains?

A UC Berkeley neurobiologist lays out the current scientific research.

Nestled in the Berkeley hills, the UC Botanical Garden contains one of the greatest collections of plants in the world. But one plant you won’t find among its rare and endangered species is cannabis.

Nevertheless, cannabis — and, specifically, its effect on the brain — was the topic of discussion on Feb. 15, part of the garden’s new lecture series on the science of cannabis.

“This is a powerful, complex, and interesting medicine,” David Presti, a neurobiologist, psychologist, and cognitive scientist at UC Berkeley, told the sold-out crowd, which included journalist and author Michael Pollan.

Presti, whose areas of speciality include the effects of drugs on the mind and body, described cannabis as “pharmakon,” a term that refers to both medicine and poison and includes all drugs. In fact, some of cannabis’ medicinal qualities — creating a psychedelic-like mental state, enhancing/altering sensory perception, intensifying emotions and thoughts, among others — can also be considered some of its less-desired effects. But cannabis is also known to be an analgesic, anti-inflammatory, anti-seizure, as well as a muscle relaxant, appetite stimulant, and sedative, among others.

Citing a 2016 study in the Journal of the American Medical Association Psychiatry, “Effects of Cannabis Use on Human Behavior,” Presti noted that the cognitive effects of cannabis include acute memory and learning impairment, but it’s less clear whether cannabis has enduring psychological impacts. There is also a question about whether cannabis use is a causative or correlative factor in educational underachievement.

The study also noted a “consistent association between adolescent cannabis use and psychosis” but that there continues to be “controversy over what proportion of psychosis risk can be attributed to cannabis use and the extent to which individuals without genetic predisposition can be precipitated into illness.” In other words, those who have risk factors for developing a psychotic condition, such as a family history of schizophrenia or severe bipolar disorder, may be at a higher risk for getting into problems by using cannabis or other powerful intoxicants. But “the idea that somebody without risk factors would be precipitated into becoming a lifelong schizophrenic from using cannabis is not something that’s supported by the evidence,” Presti said.

(There’s still a lot we don’t know about cannabis’ effects because it remains illegal at the federal level.)

To understand cannabis’ effect on our body requires an understanding of its chemistry. And cannabis, Presti said, has a unique botanical chemistry. A certain class of its chemical compounds, called cannabinoids, aren’t found in any other plants. The four most prominent cannabinoids are delta-9-tetrahydrocannabinolic acid (THCA-A), delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN). It turns out that our bodies have cannabinoid receptors, and they’re everywhere: in our neuromuscular system, enteric nervous system, endocrine system, immune system, liver and fat cells, ovaries, testicles, and even in sperm.

THC is cannabis’ primary psychoactive component. Presti explained its impact thusly: Our nervous system is made up of neurons, and these neurons are hooked together in various complex patterns. The junctions between them are called synapses. When a neuron sends a signal to another neuron, there’s a kind of “wave of electrical charge” that moves down the nerve fiber. When it gets to the end, it causes the release of a molecule — the neurotransmitter — that then goes out into the space around the neuron, called the synaptic gap. It bounces around and sticks to the receptor and that changes the function in some ways. Our brains have roughly 100 billion neurons, and we have a few hundred trillion synaptic connections between our neurons, which are active all the time. Psychoactive drugs work by sticking to receptors and “messing” with them, interfering with the normal pathway of neural signaling.

We have certain receptors in our bodies called cannabinoid receptors — so called because, at one point, THC was the only molecule anybody had been able to find that stuck to it. It turned out that these cannabinoid receptors — CB1, which is heavily present in the brain but also all over the body; and CB2, which is mostly found in the periphery of the body, especially the immune system — are more abundant than any other neurotransmitter in the brain. All vertebrate animals have them, and they’ve been discovered in invertebrates.

When THC binds to our cannabinoid receptors, it causes a whole variety of different cellular effects, including turning on and off gene expression. “It’s a whole complex universe of stuff that could be happening just with one receptor being activated in one cell,” said Presti. “Multiply times a hundred trillion different synapses and you’ve got some real complicated stuff here.”

No wonder, then, that cannabis has a whole spectrum of medicinal possibilities. And that’s only considering THC. Cannabis’ other cannabinoids also have medicinal properties.

Of course, our cannabinoid receptors don’t just exist to interact with cannabis. Our bodies produce endocannabinoids, which also activate the cannabinoid receptors in our body. In 1992, the first one was discovered. It’s called anandamide, after the Sanskrit word meaning “bliss.”

Another fascinating aspect of THC’s effect on our brains? According to Presti, THC’s effects on our CB1 receptors results in our receptors synthesizing anandamide on the spot. The process, called “retrograde signaling,” is pervasive all over the central nervous system and is an important component of regulating the strengths of the synapses. Commonly referred to as “neural plasticity,” it means our brains can change the nature of the connectivity between neurons in an ongoing, dynamic way. It’s how stroke patients can relearn to walk after the part of their brain that once controlled such movement was permanently damaged.

Presti didn’t have time to go into the other cannabinoids — such as terpenes, which are responsible for a plant’s aroma and have medicinal properties — and the receptors in our bodies that are activated by them. The herbalists, aromatherapists, and herbal medicine practitioners, he said, “are so far ahead of the science. … Don’t wait for the science to catch up — the science may take a while.”


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