These days you see signs for delta-8 THC, delta-10 THC and CBD, or cannabidiol, everywhere, at gas stations, convenience stores, vape shops and online. Many people rightly wonder which of these compounds are legal, whether they are safe to consume, and which of their supposed medicinal benefits stand up to scientific scrutiny.
The rapid proliferation of cannabis products makes it clear that the public needs to better understand what these compounds are derived from and what their actual benefits and potential risks may be.
We are immunologists who have studied the effects of marijuana cannabinoids about inflammation and cancer for more than two decades.
We see great promise in these products for medical applications. But we are also concerned that much is still unknown about their safety and their psychoactive properties.
Dissecting the differences between marijuana and hemp
Cannabis sativathe most common type of cannabis planthas more than 100 compounds called cannabinoids.
The best-studied cannabinoids extracted from the cannabis plant include delta-9-tetrahydrocannabinol, or delta-9 THC, which is psychoactive. A psychoactive substance is one that affects the functioning of the brain, altering mood, consciousness, thoughts, feelings, or behavior. Delta-9 THC is the most important cannabinoid responsible for the high associated with marijuana. CBD, on the other hand, is non-psychoactive.
Marijuana and hemp are two different varieties of the cannabis plant. In the U.S, federal regulations dictate that cannabis plants containing more than 0.3% delta-9 THC should be classified as marijuana, while plants containing less should be classified as hemp. The marijuana grown today has high levels – from 10% to 30% – of delta-9 THC, while hemp plants contain 5% to 15% CBD.
In 2018, the Food and Drug Administration approved the use of CBD extracted from the cannabis plant treat epilepsy. In addition to being a source of CBD, hemp plants can also be used commercially developing various other products such as textiles, paper, medicines, food, animal feed, biofuel, biodegradable plastic and building material.
Recognizing the potential broad uses of hemp, when Congress passed the Agriculture Improvement Act, called the Farm Bill, in 2018 it removed hemp from the controlled substances category. This made it legal to grow hemp.
As hemp-derived CBD saturated the market following Farm Bill approval, CBD manufacturers began to leverage their technical prowess to extract other forms of cannabinoids from CBD. This led to the emergence of delta-8 and delta-10 THC.
The chemical difference between delta-8, delta-9 and delta-10 THC is the position of a double bond on the chain of carbon atoms they structurally share. Delta-8 has this double bond on the eighth carbon of the chain, delta-9 on the ninth carbon, and delta-10 on the 10th carbon. These slight differences cause them to exert different levels of psychoactive effects.
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The properties of delta-9 THC
Delta-9 THC wax one of the first forms of cannabinoid to be isolated from the cannabis plant in 1964. The highly psychoactive property of delta-9 THC is based on its ability to activate certain cannabinoid receptors, called CB1, in the brain. The receptor, CB1, is like a lock that can only be opened with a specific key – in this case delta-9 THC – allowing the latter to influence certain cell functions.
Delta-9 THC mimics the cannabinoids, called endocannabinoids, that our bodies naturally produce. Because delta-9 THC mimics the action of endocannabinoids, it also affects the same brain functions they regulate, such as appetite, learning, memory, anxiety, depression, pain, sleep, mood, body temperature, and immune responses.
The FDA approved delta-9 THC as a treatment in 1985 chemotherapy-induced nausea and vomiting in cancer patients and, in 1992, to stimulate appetite in HIV/AIDS patients.
The National Academy of Sciences has reported that cannabis is effective in relieving chronic pain in adults and for improving muscle stiffness in patients with multiple sclerosis, an autoimmune disease. That report also suggested that cannabis may help sleep results and fibromyalgia, a medical condition in which patients complain of fatigue and pain throughout the body. A combination of delta-9 THC and CBD has even been used to treat muscle stiffness and spasms in multiple sclerosis. This medicine, called Sativex, has been approved in many countries but not yet in the US
Delta-9 THC can also activate another type of cannabinoid receptor called CB2, which is primarily expressed on immune cells. Studies from our laboratory have shown this delta-9 THC can suppress inflammation by the activation of CB2. This makes it very effective in the treatment of autoimmune diseases such as multiple sclerosis and colitis as well inflammation of the lungs caused by bacterial toxins.
However, Delta-9 THC is not approved by the FDA for conditions such as pain, sleep, sleep disorders, fibromyalgia, and autoimmune disorders. This has led people to self-medicate against such conditions for which no effective pharmacological treatments currently exist.
Delta-8 THC, a chemical cousin of delta-9
Delta-8 THC is in very small amounts in the cannabis plant. The delta-8 THC widely marketed in the US is a derivative of hemp CBD.
Delta-8 THC binds to CB1 receptors less potent than delta-9 THC, which makes it less psychoactive than delta-9 THC. People seeking delta-8 THC for medicinal benefits seem to prefer it over delta-9 THC because delta-8 THC doesn’t make them get very high.
However, delta-8 THC binds to CB2 receptors with a similar strength to delta-9 THC. And because activation of CB2 plays a crucial role in suppressing inflammationdelta-8 THC may be preferable to delta-9 THC for treating inflammation because it is less psychoactive.
There are no published clinical studies to date on whether delta-8 THC can be used to treat clinical conditions such as chemotherapy-induced nausea or appetite stimulation in HIV/AIDS that respond to delta-9 THC. However, animal studies from our lab have shown that delta-8 THC is effective in the treatment of multiple sclerosis.
The sale of delta-8 THC, especially in states where marijuana is illegal, has become very controversial. Federal agencies consider all compounds isolated from marijuana or synthetic forms, similar to THC, Schedule I controlled substancesmeaning they currently have no accepted medical use and have significant potential for abuse.
However, hemp manufacturers claiming that delta-8 THC should be legal because it is derived from CBD isolated from legally grown hemp plants.
The emergence of delta-10 THC
Delta-10 THC, another chemical cousin of delta-9 and delta-8, has recently hit the market.
Scientists don’t know much about this new cannabinoid yet. Delta-10 THC does also derived from hemp CBD. People have reported anecdotally feeling euphoric and more focused after consuming delta-10 THC. Anecdotally, people who consume delta-10 THC say so too produces less of a high than delta-8 THC.
And virtually nothing is known about the medicinal properties of delta-10 THC. Yet it is marketed in the same way as the other more well-studied cannabinoids, with claims of a range of health benefits.
The future of cannabinoid derivatives
Research and clinical trials of marijuana or delta-9 THC to treat many medical conditions have been stymied by their classification as Schedule 1 substances. In addition, the psychoactive properties of marijuana and delta-9 THC cause side effects on brain functions; the high that comes with it makes some people feel nauseous, or they just hate the sensation. This limits their usefulness in the treatment of clinical conditions.
In contrast, we believe that delta-8 THC and delta-10 THC, as well as other potential cannabinoids that can be isolated from the cannabis plant or synthesized in the future, hold promise. With their strong activity against the CB2 receptors and their lower psychoactive properties, we believe they offer new therapeutic opportunities to treat a variety of medical conditions.
