Healthcare Providers and Patients
Are you a healthcare provider or a patient looking for more information about the cannabis plant? Read below!
Cannabinoids
𝛥9-THC Type (25 cannabinoids)
Includes the most abundant, most well-researched, intoxicating cannabinoid, more familiarly referred to as “THC.”
THC binds to cannabinoid receptors CB1 and CB2, which are integral components of the endogenous cannabinoid system. Although THC exhibits a weaker binding affinity for CB2 receptors, it also demonstrates a strong affinity for CB1 receptors.
It is established that CB1 receptors are primarily expressed in the central nervous system (CNS), whereas CB2 receptors are found in the peripheral nervous system (PNS), immune cells, and various organs.1,2
Upon interaction with THC, the CB1 receptor elicits hypolocomotion, hypothermia, catalepsy, and analgesia responses.
THC's effects on emesis, appetite, and pain are attributed to its binding of CB1 receptors in the CNS, which modulate sensory, somatic, and cognitive perception. 3
In addition, CB2 and other receptors mediate THC's neuroprotective, anti-spasmodic, and anti-inflammatory effects.
A predominance of most state-led cannabis programs cultivate, process, and sell products that have at least moderate levels of 𝛥9-THC as the active ingredient.
The FDA has only approved three products that are synthetic 𝛥9-THC analogs:
- Marinol (dronabinol – CIII)
- Syndros (dronabinol – CII)
- Cesamet (nabilone – CII)
These drugs are approved for a variety of medical conditions, and much of the clinical evidence about 𝛥9-THC comes from the Phase I-IV studies that were conducted with these drugs in preparation for their FDA New Drug Application.
Many products, all synthetic, are also sold in ancillary markets (gas stations/vape stores) that contain some form of 𝛥9-THC or a derivative thereof.
𝛥8-THC Type (5 Cannabinoids)
Δ8-THC is a cannabinoid that is a double bond isomer of the more well-known Δ9-THC and almost as potent as native Δ9-THC.
It was first derived from the cyclization of cannabidiol (CBD), and it was discovered to be highly psychoactive in human studies (Adams, 1942).
By 1966, it was realized that Δ8-THC was present in only negligible amounts in cannabis and cannabis-derived products, such as hash (Hively et al., 1966).
Δ8-THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ9-THC
The passing of the U.S. Farm Bill in 2018 increased the sale of Δ8-THC products in the United States.
The Δ8-THC found in these products is synthetic, not plant-derived
Δ8-THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents, as well as side products of the reactions.
Subsequent research focused much more on Δ9-THC, but the effects of Δ8-THC continued to be characterized throughout the following decades, mainly due to its improved stability vs Δ9-THC (Hanuš et al., 2016)
To learn more about Δ8-THC characteristics, please see the below article: https://www.mdpi.com/1420-3049/29/6/1249
To learn about Δ8-THC byproducts and impurities, please see the below article: https://pubs.acs.org/doi/10.1021/acs.jnatprod.2c01008
- Recently, the U.S. Food and Drug Administration (FDA) issued strong warning letters on marketing products containing Δ8-THC.
- Although the FDA has neither evaluated nor approved these products for use, they are still available in stores and online, and the effects of their use have not been well described.
- Between December 1, 2020, and February 28th, 2022, the FDA received 104 reports of adverse events from patients who consumed Δ8-THC-containing products of different age groups.
- Anxiety, vomiting, dizziness, loss of consciousness, tremors, and hallucinations are examples of the reported side effects.
- Intoxication or adverse events from illicit Δ8-THC products might be exacerbated by the presence of byproduct impurities produced during the total synthesis and/or conversion of CBD to Δ8-THC.
Cannabidiol (CBD) Type (10 Cannabinoids)
- CBD is the most predominant non-intoxicating cannabinoid found in the cannabis plant and includes 10 subtypes.
- Of the potential therapeutic benefits of CBD, its use as an anticonvulsant has been studied most extensively.
- In 2018, FDA approved the first plant-derived cannabinoid medicine called Epidiolex, a 98% cannabidiol oral solution for children and adults with rare, distinct epilepsy syndromes.
Epidiolex
- The first drug in the U.S. from cannabinoids obtained from plants
- Purified Cannabidiol (CBD) in sesame oil
- Indicated for: Dravet, Lennox-Gastuat, Tuberous Sclerosis Complex
TIMELINE:
2007– GW Pharmaceuticals begins development
2013– First clinical trials
2018– Approved in US: C-V
2019– 2018 Farm Bill excludes certain cannabinoids from CSA
2020– Epidiolex de-scheduled by DEA
UM CBD Oral Solution
- Developed at UM for UMMC clinical study
- Full-spectrum Cannabis Extract in sesame oil - CBD: THC 20:1
2014– Legislature passes Harper Grace’s Law for UM/UMMC treatment of young epilepsy patients
2017– UMMC pediatric neurologist Brad Ingram submits IND to FDA Notice to Proceed from FDA. The study begins with 10 patients.
2019– FDA extends study after promising results reported.
2024- Study continues
Cannabinol (11 compounds)
CBN, a major constituent of cannabis, is a non-psychotropic cannabinoid and a natural constituent identified in C. sativa formed by a non-enzymatic oxidation by-product of ∆9-THC, following an extended period of storage, essentially under elevated temperatures (Huestis, 2005, Murphy et al., 1990)
CBN exhibits a variety of pharmacological properties, including anticancer, antimicrobial, analgesic, and anti-inflammatory activities
To learn more about the potential health effects of CBN, read the article below:https://www.sciencedirect.com/science/article/pii/S0926669024003364
Cannabigerol (16 compounds)
Cannabichromene (9 compounds)
https://pubmed.ncbi.nlm.nih.gov/32431186/
Twenty-five CBD products were analyzed for label claim, actual CBD content, percent of label claim, THC content > 0.3%, and the presence of synthetic cannabinoids were analyzed and reported.
Twenty-two products contained measurable quantities of CBD (3 were devoid of phytocannabinoids)
Of the 22, total quantities per container varied greatly:
One contained only 0.02 mg CBD, while another contained 786 mg
Five products made no label claim for CBD, two of which contained 17 mg and 0.02 mg, while the other three contained no measurable CBD.
For the 20 products that made a label claim for CBD, values for percent label claim ranged from 0.06%-168%
Only 3 products were within ±20% of the label claim for CBD, while 13 were <50% of the claim.
Three products contained THC that exceeded 0.3% (one contained 45% THC).
More disconcerting was the fact that 4 products were adulterated with synthetic cannabinoids.
Ancillary Marketplace
Cannabidiol (CBD), the most predominant non-intoxicating cannabinoid, is being produced by hemp farmers pursuant to the 2018 Farm Bill.
Due to a perceived and unchallenged loophole, CBD biomass is chemically converted/synthesized by hemp manufacturers into uber-potent, intoxicating, manufactured products – without any regulatory oversight or enforcement.
These products are then sold into commerce to unsuspecting adults and children as “Delta” or Hemp without proper scientific validation or toxicology studies.
This is particularly concerning given there are a number of scientific studies and, most recently, concerns raised by both the DEA and FDA that synthetic cannabinoids can be dangerous, even lethal
Two Issues with language in the bill:
- “ALL DERIVATIVES … WHETHER GROWING OR NOT”
The fact that some compounds may exist in trace, coincidental amounts in nature is neither a guarantee of their safety in larger quantities nor justification for them to be considered legal “hemp derivatives” when manufactured through chemical conversion into commercially viable quantities.
The harmful reality is that the predominant amount of intoxicating hemp cannabinoids in the marketplace are derivatives and isomers.
The unintended result of the definition of hemp was the creation of a federally protected, unregulated industry of intoxicating hemp-derived cannabinoids carved out of the Controlled Substances Act.
- “NOT MORE THAN 0.3 PERCENT ON A DRY WEIGHT BASIS.”
The function of escalating weight allowance of 0.3 percent delta-9 THC by dry weight is not an indication of non-intoxication.
Note the correlation to when the 2018 Farm Bill was passed, which spurred the proliferation of these products into the marketplace.
State poison control centers also report similar data and that “90% of the calls are about accidental ingestions by children and adolescents.”
These products are often packaged colorfully and seem targeted toward children.
In particular, edible products are sold as gummies, cookies, brownies, crisps, etc., which could potentially attract children more than other formulations, such as inhalation or liquid products.
Cannabicyclol (3 compounds)
Cannabielsoin (5 compounds)
Cannabinodiol (2 compounds)
Cannabitriol (9 compounds)
30 compounds