Marijuana (Cannabis)

Delta-8 THC (Δ-8 THC)

Delta-8 THC (Δ-8 THC) is a relatively recently discovered and lesser-known hemp-based cannabinoid that is gaining popular attention as a milder version of delta-9 THC, the dominant cannabinoid found in marijuana that is responsible for generating the “high” associated with the uses of marijuana. It is currently legal in most states but there are a few states that have started what may be a trend towards making it illegal.

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Definitions and Terms Related to Pain

 

Delta-8 THC (Δ-8 Tetrahydrocannabinol)

 

What is Delta-8 THC?

Delta-8 THC (Δ-8 THC) is a minor cannabinoid which is generally considered to be a milder version of delta-9 THC ( Δ-9 THC), the primary form of THC found in cannabis. Only Δ-8 THC,  Δ-9 THC, and their hydroxyl metabolites (breakdown products) are psychoactive and produce the euphoric high generally sought by recreational users of marijuana. However, along with CBD, many of the clinical therapeutic benefits obtained from marijuana also come from these cannabinoids.

 

The delta-8-THC craze started as the result of an oversupply of CBD extracted from US-grown hemp which caused the price of CBD to plummet. Producers began looking for ways to turn the over-supply of CBD into something profitable

 

What are the Benefits Offered by Using Δ-8 THC?

Essentially, the benefits of Δ-8 THC are the same but less intense compared to Δ-9 THC. These benefits include psychoactive effects, reduction of pain, suppression of nausea and vomiting and stimulation of appetite.

 

Psychoactive Effects

The psychoactive effects experienced with Δ-8 THC are considered mild, described as slightly euphoric, mentally stimulating and energizing. Anxiety and paranoia are generally absent.

 

Suppression of Nausea

The “grandfather of medical marijuana, Dr Raphael Mechoulam, carried out a study in 1995  where delta-8-THC was administered to eight children aged from 3 to 13 with various hematologic cancers treated with chemotherapy. The children treated with delta-8-THC completely eliminated vomiting and reduced the side effects of chemotherapy to negligible levels while being well tolerated.

 

How Do People Use Δ-8 THC?

Based on an online survey of Δ-8 THC consumers, patterns of Δ-8 THC use has both similarities with and differences from the use of Δ-9 THC cannabis and products. Administration methods are primarily edibles (64%) and vaping concentrates (48%). Other methods include sublingual use, administered and absorbed under the tongue, such as oils and tinctures.

 

About half of the participants (51%) use Δ-8 THC to treat medical conditions, primarily anxiety or panic attacks (69%), stress (52%), depression or bipolar disorder (46%), and chronic pain (41%). Survey participants compared Δ-8 THC very favorably with both delta-9-THC and prescription medications, often substituting Δ-8 THC for either or both. Users of delta-9-THC often report a clearer mind and more energetic mood when using delta-8 THC. 

 

The Safety of Δ-8 THC

The safety of Δ-8 THC use has not been established nor has the safety of vape blends.  Δ-8 THC is often marketed in edible forms, as cartridges of vape blends or sprayed onto hemp flowers which are then smoked or vaped. Using Δ-8 THC is much less likely to trigger severe anxiety or paranoia compared with Δ-9 THC so it appears safer for use. Unfortunately there are no long term studies evaluating the safety of long term or repeated use of Δ-8 THC.

 

How is Δ-8 THC Produced?

Δ-8 THC was discovered in the early 1970s but has only achieved popular interest in the last year or two. The reason it’s not as popular as Δ-9 THC or CBD — despite being psychotropic — is that it’s only present in cannabis in very low concentrations, about 0.01% – 0.1% in most marijuana plants. There are reports of plants containing as much as 1%, but they are exceptions. Economical extraction of delta-8-THC from cannabis requires levels of about 15–20%. Since using it for therapeutic purposes requires concentrated products, some modern growers have developed different breeding and extraction techniques to obtain greater quantities of this cannabinoid naturally. 

 

However, because Δ-8 THC generally occurs in only trace amounts in hemp, it’s generally obtained by chemical synthesis. Getting a substantial amount of Δ-8 THC requires using specialized extraction, conversion, isolation, and refinement processes. There are several processing methods available, but one of the most feasible ones is to convert cannabidiol (CBD) into Δ-8 THC, which gives higher yield and purity than other methods. This process involves various steps that allow extractors to purify and isolate Δ-8 THCt without residual solvents and impurities.

 

Processing Safety

The method of processing is important because sub-standard processing can leave toxic solvents and impurities mixed with the Δ-8 THC.  Chemists are sounding the alarm after finding several unidentified compounds in products labeled as delta-8-THC.  A lot of irresponsible production is being performed by many people that are getting their information from online forums, and many of them aren’t necessarily trained chemists.

 

The conversion of cannabidiol into delta-8-THC also produces small amounts of delta-9-THC and delta-10-THC.  Little is known about the effects of delta-10 THC, although users report feeling euphoric and more focused when using it. There seems to be less concern about the THC isomers delta-8 THC and delta-10 THC then the other unidentified compounds and impurities. Delta-8, delta-9, and even delta-10 don’t seem to have any serious side effects that are known yet.

 

Because there is no government regulation overseeing production of Δ-8 THC, it is highly recommended to purchase Δ-8 THC only from reputable sources that provide independent certificates of analysis (CoA) that verify the purity of the Δ-8 THC product. Be aware that some of  the by-products produced in the manufacture of Δ-8 THC  are unidentified, the CoA are not completely reliable means of identifying potentially dangerous impurities. Existing independent analytical labs can’t handle the burden of exhaustive testing on all delta-8-THC products at this time. Don’t purchase Δ-8 THC products from gas stations, convenience stores or unreliable sources.

 

Although the legal environment is questionable, current knowledge suggests that Δ-8 THC may be equally effective for desired benefits compared with cannabis use but with less undesirable adverse effects. More research is needed to verify the safety and effectiveness of  Δ-8 THC.

 

Δ-8 THC vs. Δ-9 THC vs. Δ-9 THC: What’s The Difference?

The fundamental difference is that Δ-8 THC has a lower  potency than Δ-9 THC. This means that the therapeutic benefits – and the side effects  –  are much the same between the two but they are weaker with Δ-8 THC. The main difference between Δ-8 THC and Δ-9 THC is in their psychotropic effects — Δ-8 THC doesn’t provide the same degree of mental stimulation as Δ-9 THC does. Research suggests that Δ-8 THC has only two-thirds or less of the potency of Δ-9 THC while others report it to be 50% less potent and in some cases 3-10 times less potent. Δ-8 THC is reported to give a more clear-minded euphoric effect with much less anxiety — even if used in higher doses.

Regarding Δ-10 THC, it appears similar to Δ-8 THC, but even less potent. As to whether these reduced potencies of Δ-8 THC and Δ-10 THC also applies to their other therapeutic benefits, it is unclear but appears likely.

 

Chemical Differences Between Δ-8 THC and Δ-9 THC 

In terms of chemistry, Δ-8 THC and Δ-9 THC are very similar compounds. Tetrahydrocannabinol (THC) has different structural forms known as chemical analogs. Analogs are compounds with a similar structure to another compound, but different in certain aspects. In this case, delta-8 and delta-9 are double bond chemicals — hence the delta in their names. The only difference is that delta-9 THC has a double bond on the 9th carbon of the chain, whereas delta-8 has it on the 8th. This is important because it causes each compound to interact differently with the receptors in the endocannabinoid system.

 

Vaporization Temperatures:

Delta-8 THC: 352• F (178• C)

Delta-9 THC: 315• F (157• C)

 

How Does Δ-8 THC Work?

Δ-8 THC, like Δ-9 THC, binds to the cannabinoid receptor CB1, located primarily in the central nervous system. The CB1 receptor is responsible for the euphoric effects produced by these compounds as well as the neuroprotective effects and relief from nausea and pain. Δ-8 THC, like Δ-9 THC, also binds with CB2 receptors, which help regulate the immune system.

 

Although more research is needed, Δ-8 THC may have neuroprotective properties by increasing the levels of acetylcholine in the brain, a neurotransmitter that plays an important role in learning and memory. Low levels of acetylcholine are associated with conditions that cause memory loss and related symptoms including dementia and Parkinson’s disease.

 

Transdermal Δ-8 THC

A 2004 study quantified the transdermal penetration of Δ-8 THC, cannabidiol (CBD) and cannabinol (CBN) as likely candidates for transdermal combination therapy. Tissue concentrations of Δ-8 THC were significantly higher than for CBN. Lag times for CBD were significantly smaller than for CBN. The permeabilities of CBD and CBN were 10-fold higher than for Δ-8 THC. Future studies for improved transdermal delivery were advised.

 

Metabolism of Δ-8 THC

Delta-8 THC is mostly transformed into hydroxy-11-Δ-8 THC when it passes through the liver after being absorbed from the g.i tract when swallowed. Hydroxy-11-8 THC is believed to be psychoactive like Δ-8 THC but its other therapeutic benefits, if any, are not known. It may be analogous to hydroxy-11-Δ-9 THC which is considered somewhat more psychoactively potent than Δ-9 THC but otherwise its therapeutic benefits remain unknown.

 

Δ-8 THC in Botanical Cannabis

Delta-8 THC, like delta-9 THC, is an analog of tetrahydrocannabinol (THC) that naturally occurs in cannabis but unlike delta-9 THC,  delta-8 THC is present only in in trace amounts, typically about 0.01%.  Cannabinoids are synthesized and stored predominantly in glandular trichomes which are hair-like epidermal protrusions densely concentrated in the flowers of cannabis plants. Enzymes convert the “mother” of all cannabinoids, cannabigerolic acid (CBGA), into THC’s precursor, tetrahydrocannabinolic acid (THCA). During the process of decarboxylation, losing a CO2 molecule, which is associated with long-term storage or application of heat, THCA transforms into delta-9 THC, which with aging it oxidizes and is  converted into delta-8 THC.

Will Taking Δ-8 THC Make One Fail a Drug Test for Marijuana?

Yes, one will most likely fail a drug test after consuming Δ-8 THC because a standard drug test is likely to detect delta-8 THC or its metabolites and interpret it as recent use of Δ-9 THC. A standard urine drug test may even have a lower cutoff level of delta-8 THC compared to delta-9 THC. The cutoff level is the concentration of the compound in fluid that’s required for the test to be positive. In an example test, the cutoff level of the main delta-9 THC metabolite is 50 ng/mL, while the delta-8 THC metabolite is detected at 30 ng/mL. The length of time delta-8 THC stays in the body depends on several factors, including:

  1. Amount of body fat a person has
  2. Frequency of consumption of delta-8 THC
  3. Whether the user is combining different components
  4. The sensitivity of the drug test (more sensitive tests can detect lower doses)

 

THC-O

Another THC variant that is getting attention is “THC-O,” which is another cannabinoid, THC-O-acetate, the acetate ester of THC. This compound is now popping up in gummies and vapes. THC-O does not occur naturally in cannabis plants. Currently there are no human studies on the effects or safety of acetylated THC and even less is known about THC-O than about Δ-8 THC. As such it is not recommended at this time to take THC-O. in any form.

Resources:

National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

 

www.Healer.com

This website appears to be good resource for exploring medical marijuana.

 

References:

   

Delta-8 THC – Overviews

  1. Delta-8-THC – Delta-9-THC’s nicer younger sibling? – 2022
  2. Consumer Experiences with Delta-8-THC Medical Use, Pharmaceutical Substitution, and Comparisons with Delta-9-THC – PubMed 2022
  3. Human skin permeation of Delta8-tetrahydrocannabinol, cannabidiol and cannabinol – PubMed – 2004

 

 

Cannabinoids – Pain

  1. Association of Cannabinoid Administration With Experimental Pain in Healthy Adults – 2018
  2. Effects of Cannabinoid Administration for Pain – A Meta-Analysis and Meta-Regression – 2019
  3. Cannabis-based medicines and the perioperative physician – 2019
  4. Cannabis‐based medicines for chronic neuropathic pain in adults – 2018
  5. Cannabinoids in the Descending Pain Modulatory Circuit- Role in Inflammation – 2020
  6. Current Evidence of Cannabinoid-Based Analgesia Obtained in Preclinical and Human Experimental Settings – PubMed – 2018
  7. Role of Cannabinoids and Terpenes in Cannabis-Mediated Analgesia in Rats – PubMed – 2019
  8. Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain – An Update on Current Evidence and Cannabis Science – 2018
  9. The Molecular Mechanisms That Underpin the Biological Benefits of Full-Spectrum Cannabis Extract in the Treatment of Neuropathic Pain and Inflammation – PubMed – 2020
  10. Cannabis sativa L. an
    d Nonpsychoactive Cannabinoids – Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer – 2018
  11. Cannabinoid Delivery Systems for Pain and Inflammation Treatment – 2018
  12. Cannabinoid Formulations and Delivery Systems – Current and Future Options to Treat Pain – 2021

 

CBD – Interaction with THC

  1. Cannabidiol: a promising drug for neurodegenerative disorders? – PubMed – NCBI
  2. Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis – 2015
  3. Taming THC – potential cannabis synergy and phytocannabinoid-terpenoid entourage effects – 2011
  4. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI

 

 

Cannabinoids: Tetrahydrocannabivarin (THCV):

  1. The phytocannabinoid, Δ9-tetrahydrocannabivarin, can act through 5-HT1A receptors to produce antipsychotic effects – 2015

 

Medical Marijuana –Misc

  1. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  2. Cannabis and cannabis extracts – greater than the sum of their parts? – 2001
  3. Medical cannabis and mental health: A guided systematic review. 2016 – PubMed – NCBI
  4. Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. – PubMed – NCBI
  5. Cannabis-conclusions – 2017 National Academy of Sciences
  6. Cannabis-chapter-highlights – 2017 National Academy of Sciences
  7. Cannabis-report-highlights – 2017 National Academy of Sciences
  8. Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Bene ts of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?-2004
  9. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. – PubMed – NCBI
  10. Cannabis use and cognitive function: 8-year trajectory in a young adult cohort. – PubMed – NCBI
  11. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. – PubMed – NCBI
  12. Cannabinoids and Cytochrome P450 Interactions. – PubMed – NCBI Pharmacogenetics of Cannabinoids – 2018
  13. Systematic review of systematic reviews for medical cannabinoids – 2018
  14. Adverse effects of medical cannabinoids – a systematic review – 2008
  15. Cannabimimetic effects modulated by cholinergic compounds. – PubMed – NCBI
  16. Antagonism of marihuana effects by indomethacin in humans. – PubMed – NCBI
  17. Pharmacokinetics and pharmacodynamics of cannabinoids. – PubMed – NCBI
  18. Clinical Pharmacodynamics of Cannabinoids – 2004
  19. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. – 2017
  20. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
  21. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. – PubMed – NCBI
  22. Pharmacology of Cannabinoids
  23. Current-status-and-future-of-cannabis-research-Clin-Researcher-2015
  24. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems – A Clinical Review – 2015
  25. Cannabis Use in Patients with Fibromyalgia – Effect on Symptoms Relief and Health-Related Quality of Life – 2011
  26. Weighing the Benefits and Risks of Medical Marijuana Use – A Brief Review – 2018
  27. A Marijuana-Drug Interaction Primer – Precipitants, Pharmacology, and Pharmacokinetics – 2019
  28. Myorelaxant Effect of Transdermal Cannabidiol Application in Patients with TMD – A Randomized, Double-Blind Trial – 2019
  29. Drug interactions with cannabinoids – 2020
  30. The effects of acute and sustained cannabidiol dosing for seven days on the haemodynamics in healthy men – A randomised controlled trial – 2019
  31. Novel approaches and current challenges with targeting the endocannabinoid system – 2020
  32. Herbal Preparations of Medical Cannabis – A Vademecum for Prescribing Doctors – 2020
  33. Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis – A randomized controlled trial – 2020
  34. Practical Strategies Using Medical Cannabis to Reduce Harms Associated With Long Term Opioid Use in Chronic Pain – 2021
  35. Endocannabinoid Levels in Ulcerative Colitis Patients Correlate With Clinical Parameters and Are Affected by Cannabis Consumption – 2021
  36. The pharmacokinetics and the pharmacodynamics of cannabinoids – 2018

 

Medical Marijuana – Product Evaluation

  1. Recommended methods for the identification and analysis of cannabis and cannabis products – 2009
  2. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018
  3. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
  4. Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements – 2020

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