Cannabinoids: A Brief Excursion into Neuropharmacology

Thom Thompson

Thom Thompson

Editor

One of the first things to learn about cannabis is that nobody knows much for sure about it; not about its botany, chemistry or uses. This article brings you a quick overview of a few biochemical aspects of cannabis for human consumption and use.   

Knowledge about the plant and understanding of its potential uses are rudimentary at best. Only with the enactment of the two U.S. Farm Acts in the last decade has there been meaningful funding of any kind of research into cannabis by the federal government. And that research focuses on industrial hemp – cannabis for non-psychoactive uses.  

There has long been some minor funding of research into cannabis, since the attractiveness of cannabis for providing intoxication was unavoidable. Researchers wanted to know how and why marijuana affected people. Cannabiniol (CBN) was discovered in 1940. THC, another compound found in all cannabis plants, was identified in 1942 as the component of the plant that provides users a temporary euphoric high accompanied by few side effects. 

“Marijuana” refers to those parts of a cannabis plant that contain high amounts of THC that can be accessed and consumed relatively easily, for example the flower of the plant. High THC derivatives of cannabis plants that no longer resemble their plant source are also referred to as marijuana: “marijuana edibles,” for example.

In total, there are approximately 560 different chemical compounds in cannabis plants. THC is one of about 115 cannabinoids that have been identified in cannabis plants. Cannabinoid refers to any chemical substance that joins to cannabinoid receptors in the human body.

CBN, CBD and THC, the first cannabinoids to have been identified – in that order, at first were thought by medical researchers to pass into the brain tissue directly. It was not until the mid 1980s that specialized cannabinoid “receptors” were identified in human cells in the nervous system. “CB1” and “CB2” are the only receptors conclusively identified so far, but there is a growing consensus that there are more of them. 

THC interacts with CB1 receptors to interfere with normal signals, producing the “high” sensation. The processes by which it affects the human nervous system are pretty well understood. 

How CBD, the cannabis plant’s most prevalent cannabinoid, interacts with cannabinoid receptors and with other cannabinoids has not been identified. So far, though, it is thought that CBD interacts far less than THC with either the CB1 or CB2 receptors. 

Sold even at Walmart, CBD has met with considerable commercial interest. When derived from low-THC cannabis plants (hemp, in other words), it is almost fully legal for sale and consumption in the U.S. as a result of the 2018 Farm Act. 

That law also directed the Food and Drug Administration to study CBD and determine whether and how it should be regulated. So far, the agency has limited its actions to warning letters to producers regarding efficacy claims and mislabeling of contents.

A long list of benefits has been attributed to using CBD both as an ingested quasi-medicine and as a topical treatment. CBD is thought by some to interact with THC so as to block certain of its effects and also to heighten others when they are consumed together. But there is little or no research that backs – or refutes – those claims. 

Probably largely as a result of a 2013 CNN report on the efficacy of high-CBD, low THC in treating epilepsy, CBD enjoys a reputation for being calming and effective as a sleep aid. So far, these effects have not been demonstrated conclusively by researchers. Leafly, a major online cannabis products retailer, even says on its website about CBD as a sleep aid: 

Depending on who you ask, CBD has been reported as having either a stimulating or a calming effect, thus adding confusion to the overall equation. While there is very little published evidence regarding dosing, research to date indicates that at higher doses, CBD has a calming effect; yet at lower doses, CBD has a stimulating effect.

(Well that settles that.)

There is a small handful of recognized CBD medications. The FDA has approved CBD-based Epidiolex for use in rare drug-resistant types of childhood epilepsy. The recommended dosage of 10-20 mg/kilogram of body weight is far above what over the counter consumer-friendly CBD products recommend. In Canada and New Zealand, CBD medications have been approved for use in treating symptoms of multiple sclerosis. 

And then there is the cannabinoid that was discovered first in 1940, CBN. CBN is closely associated with THC.  Both CBN and THC are created in the cannabis plant from the same forerunner chemical, THC-a. CBN also is created by aging or degrading THC. It may have slight similar psycho-active attributes, which could be causing the current buzz about it.

The 2018 Farm Act permits interstate commerce in all cannabinoids except THC. CBN might be the basis for attractive tradable products in states that limit recreational or medical marijuana. At the same time, the effects of CBN on the human nervous system are even less well researched and understood than CBD and there are few if any experience with the potential side effects of the high-dose CBN-based recreational products that might be substituted for marijuana. 

Finally, remember that there are still another 112 or so cannabinoids left to research after these three, which themselves are not very well understood. 

 

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