User:Birmaniahern/Delta-8-Tetrahydrocannabinol

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Background

Delta-8-Tetrahydrocannabinol, also known as, delta-8-THC, Δ⁸-THC, is a psychoactive cannabinoid derived from the cannabis Sativa plant. It is an isomer of delta-9-tetrahydrocannabinol (delta-9-THC, Δ⁹-THC), the compound commonly known as THC. ∆⁸-THC is under preliminary research for its biological properties. Delta-8-THC has not been approved by the FDA thus far for public use and should not be used around children or pets.

Legality in the United States

In 1937, Delta-9 THC was made illegal with the passage of the Marijuana Tax Act, which made cannabis illegal on a federal level. Over the course of the 1970s, 11 states decriminalized marijuana, with others reducing penalties. In 1976, the start of a parent’s movement that influenced their concerned emotions and questions, that led to the War on Drugs in the 1980s.

The 2018 United States farm bill signed into law in December 2018 states that, "Any cannabis containing under 0.3% Delta-9 THC is classified as 'hemp' and no longer a controlled substance." ∆⁸-THC products partially synthesized from compliant sources (including industrial hemp and derivative cannabidiol extracts) have been sold by a wide variety of digital vendors and a more limited array of brick and mortar retailers. Ranging from bulk quantities of unrefined distillate to prepared edibles and atomizer cartridges suffused with cannabis-derived terpenes, are usually marketed as federally legal alternatives to their ∆⁹-THC counterparts. However, the legal status of ∆⁸-THC at the federal level is in question with some believing that the Oct. 2020 DEA IFR addressing "synthetics" applied to Delta-8 and other hemp derivatives allowed by the Farm Bill. While most states have legalized ∆⁸-THC, a handful have not leading to confusion as to whether or not it should be legalized.

Beginning in late 2020, ∆⁸-THC began to attract the attention of many cannabis consumers throughout the United States. Thought of as an alternative to traditional cannabis use, especially in areas where marijuana is illegal, the news of ∆⁸-THC spread quickly via multiple media platforms which attracted a storm of social media attention. With ∆⁸-THC starting to attract the attention of people, it has made it easy for smoke shops and dispensaries to start carrying ∆⁸-THC infused edibles and atomizer cartridges for individuals to purchase.

Because marketing of ∆⁸-THC products does not require special licensing, the fact that these products can be produced and marketed nationally instead of one state at a time, and have no more tax than an ordinary sales tax, means that they are far cheaper than ∆⁹-THC products purchased in a cannabis dispensary. They can be sent through the mail; ∆⁹-THC products, still illegal at the federal level, can not. As of 2021, a sizeable new industry, including franchises, is being or has already been created.

As of early 2021, Delta-8/∆⁸-THC is one of the fastest growing segments of products derived from hemp. Delta-8-THC products have been sold in regulated recreational cannabis and medical cannabis industries within the United States for over one year.

Effects

∆⁸-THC is moderately less potent than Δ⁹-THC meaning that it has properties similar to those of ∆⁹-THC, although to a lesser degree per milligram of material consumed. Delta-8-THC and delta-9-THC both contain a double bond in their molecular chain, but the location is different. Delta-8-THC has the bond in the 8th carbon chain while delta-9 contains it in the 9th carbon chain.

Although delta-8-THC functions similarly to delta-9 in many ways, it appears to be only two-thirds as psychoactive. This may be because it bonds differently to CB1, the cannabinoid receptor that regulates much of THC’s mind-altering effect. ∆⁸-THC may cause increased heart rate, reddening of the eyes, dizziness, dryness of the mouth and throat, paresthesia, tinnitus, increased body awareness, weakness, muscle tension or tremor, reduced motor coordination, fatigue, sleepiness, changes in visual perception, altered visual imagery, enhancement of colors or contrasts, time distortion, changes in auditory perception, euphoria, tranquility, relaxation, racing thoughts, dreamy introspective states, or difficulty in thinking, speaking, reading, or remembering.

A 1973 study testing the effects of ∆⁸-THC in dogs and monkeys reported that a single oral dose of 9,000 milligrams per kilogram of body mass (mg/kg) was nonlethal in all dogs and monkeys studied. The same study reported that the median lethal dose of ∆⁸-THC in rats was comparable to that of ∆⁹-THC. Both isomers of THC have been found to cause a transient increase in blood pressure in rats, though the effects of cannabinoids on the cardiovascular system are complex. Animal studies indicate that ∆⁸-THC exerts many of its central effects by binding to cannabinoid receptors found in various regions of the brain, including the cerebral cortex, thalamus, basal ganglia, hippocampus, and cerebellum.

Many adults experience pain once they start to grow older. Certain adults get prescribed opiates and other pain medications to help manage their pain. In a 2009 study, evidence showed that ∆⁸-THC is moderately effective in treating chronic pain adult, but eventually do cause serious side effects later down their lifespan if exposed to it . Many adults also are diagnosed with intense psychological disorders or anxiety disorders. In a 2019 study conducted in Canada experimenters wanted to test if ∆⁸-THC was effective in treating anxiety disorders. Results of this study showed that consuming ∆⁸-THC was correlated significantly with high chances of developing an anxiety condition, but was not correlated with developing generalized anxiety disorder, panic disorder, or social anxiety disorder .

∆⁸-THC can also be used to treat chronic pain in adults. Studies show that many people in the United States have to pay about $600 billion in health care expenses and lost labor. This was resulting in pharmacotherapies for adults that felt the need to have cannabinoids. A 2019 study testing the effects of ∆⁸-THC on adults showed a medium to large effect on pain reduction while the placebo produced a small effect with pain reduction . Human studies have shown that effects of ∆⁸-THC lower or reduce chronic pain for adults, but more research needs to be conducted because chronic pain differs for each person.

Research

∆⁸-THC has been studied as a potential treatment for glaucoma, corneal injury, and chemotherapy-induced nausea and vomiting.

Although ∆⁸-THC is a minor constituent of medical cannabis, no large clinical studies have been conducted on it alone. However, thus far the pharmacology of the compound has been found to be similar to its isomer delta-9-THC, though with less potency.

∆⁸-THC offers pain relief, digestive benefits and relaxation. There hasn't been much evidence that it offers pain relief to most people, exclusively adults. Digestive benefits help with excess vomiting and nausea, but, it will cause alerted hunger in people that consume ∆⁸-THC.

Physical and Chemical Properties

∆⁸-THC is a tricyclic terpenoid. Although it has the same chemical formula as ∆⁹-THC, one of its carbon-carbon double bonds is located in a different position. This difference in structure increases the chemical stability of ∆⁸-THC relative to ∆⁹-THC.

While ∆⁸-THC is naturally found in plants of the Cannabis genus, this compound can also be produced in an industrial or laboratory setting by exposing CBD to acids and heat. Solvents that may be used during this process include methylene chloride, toluene, and hexane. Acids that may be used include tosylic acid, indium(III) triflate, trimethylsilyl trifluoromethanesulfonate, hydrochloric acid, and sulfuric acid. Because it is possible for chemical contaminants to be generated during the process of converting CBD to ∆⁸-THC, such as Δ¹⁰-THC, 9-OH-HHC and other side products, as well as the potentially toxic chemical reagents used during manufacture, concern has been raised about the safety of untested or impure ∆⁸-THC products.

The ongoing controversy regarding the legal status of ∆⁸-THC in the U.S. is complicated by chemical nomenclature. According to a 2019 literature review published in Clinical Toxicology, the term "synthetic cannabinoid" typically refers to a full agonist of CB₁ and CB₂ cannabinoid receptors. According to the review, "The psychoactive (and probably the toxic) effects of synthetic cannabinoid receptor agonists are likely due to their action as full receptor agonists and their greater potency." Because ∆⁸-THC and ∆⁹-THC are partial agonists of cannabinoid receptors, rather than full agonists, these compounds are less potent and less toxic than many synthetic cannabinoids.

Pharmacodynamics

The pharmacodynamic profile of ∆⁸-THC is similar to that of ∆⁹-THC. It is a partial agonist of CB₁ and CB₂ cannabinoid receptors with about half the potency of ∆⁹-THC in most but not all measures of biological activity. ∆⁸-THC has been reported to have a K_i value of 44 ± 12 nM at the CB₁ receptor and 44 ± 17 nM at the CB₂ receptor. These values are higher than those typically reported for ∆⁹-THC (CB1 Ki = 40.7 nM) at the same receptors, indicating that ∆⁸-THC binds to cannabinoid receptors less efficiently than ∆⁹-THC.

Pharmacokinetics

The pharmacokinetic profile of ∆⁸-THC is also similar to that of ∆⁹-THC. Following ingestion in humans, hepatic cytochrome P450 enzymes including CYP2C9 and CYP3A4 first convert ∆⁸-THC into 11-hydroxy-Δ⁸-tetrahydrocannabinol (11-OH-Δ⁸-THC). Next, dehydrogenase enzymes convert 11-OH-Δ⁸-THC into 11-nor-Δ⁸-tetrahydrocannabinol-9-carboxylic acid (11-nor-Δ⁸-THC-9-COOH, also known as Δ⁸-THC-11-oic acid). Finally, Δ⁸-THC-11-oic acid undergoes glucuronidation by glucuronidase enzymes to form 11-nor-Δ⁸-tetrahydrocannabinol-9-carboxylic acid glucuronide (Δ⁸-THC-COOH-glu). This final product is then excreted in the urine.

Side Effects, Risks and Safety Concerns

∆⁸-THC is typically synthesized from cannabidiol extracted from hemp as the natural quantities of Delta 8 found in hemp are low. As a result, most products sold as ∆⁸-THC are not actually pure ∆⁸-THC. Little is known about the identity and the health effects of the impurities.

When using ∆⁸-THC, there are some minor side effects that one may experience when using. When using, one may experience dry mouth, fatigue and red eyes. ∆⁸-THC can be used in a variety of ways such as disposable vapes, edibles and atomizer cartridges. People that consume ∆⁸-THC edibles are more likely to experience severe side effects as compared to other methods of ingesting. When ingesting, one may also experience the "munchies". This stimulates one's appetite and makes them eat food uncontrollably. One will consume large portions of food compared to what an average person would eat in a day.

People can become addicted to ∆⁸-THC and develop long-term effects that impact their health. Long term effects of ∆⁸-THC include damage to the liver, depression, paranoia, memory and processing problems, cardiac problems and sometimes cancer in people.

The FDA has reported 104 adverse event reports related to delta 8 THC, including one pediatric case with a coded outcome of "death". National poison control centers received 2,362 exposure cases of delta-8 THC products between January 1, 2021 (i.e., date that delta-8 THC product code was added to database), and February 28, 2022, 58% of these exposures involve adults.

Summary with Peer Review Suggestions

Eresha8: Reworded While most states have legalized ∆⁸-THC, a handful have not leading to confusion to While most states have legalized ∆⁸-THC, a handful have not leading to confusion as to whether or not it should be legalized. Added another reference per her request but will continue to add more references, especially meta-analyses.

Denisej 2: Stated the same as Eresha8 and wants more neutral words incorporated into my article; still continuing to work on that throughout my article. I feel like I have neutral language throughout the article, but I will continue to work on this while editing the article

Hkhan11: Went into detail with how Delta-8 affects anxiety disorders in depth in the effects section. Also added a part in the research behind other effects of human behavior