The Chemistry of Delta-8 ‘New and Improved’ THC

For those who follow our bizarre concoction of drug laws, it should come as no surprise that they are both ineffective and also woefully ill-equipped to keep up with new (sometimes) legal analogs that even a marginally trained chemist can do. As I wrote about fentanyl analogs, chemistry, specifically synthetic organic chemistry (1), can easily be used to get around the law.

Rather than bore you with a tome about the legality of marijuana and marijuana chemicals, I thought I'd bore you with a chemistry lesson instead. Get ready. Here it comes! It's been a while, so I made this one especially incomprehensible. Let TDCLFH^® begin!

Nomenclature - The bane of our existence

Chemistry nomenclature, the tedious process of naming chemicals, is a baffling array of multiple naming systems, dozens of different names for the same chemical (2), and incomprehensible rules. This can be illustrated quite "nicely" by looking at how delta-8 THC, a chemical that has recently been in the news, gets its name. This should give you a pretty good idea of why nomenclature drives chemists nuts. (For clarification, you should know that delta-9 – the primary THC isomer in marijuana – is commonly known as THC. The names are interchangeable)

What Does the 8 in Delta-8 Mean?

If you have any propensity toward anxiety or self-harm, you might want to skip this. The figures below show the (apparent absence of) logic behind the number 8. Figure A (left) starts off making at least some sense.

Each carbon is assigned a number, which is necessary for assigning a name to a unique structure. The carbon atom at 12:00, which is attached to a hydroxyl group (green square), is called #1. From there, proceeding counterclockwise, the numbers assigned to the next carbon atoms increase logically – 2, then 3, then 4. Then 5, right? Nope.

Figure B shows that the position after #4 is ... #10b (blue). Huh? How can this be? Answer: you don't want to know. Continuing, #5 gets assigned to the oxygen atom next to 10b. No big deal. We're still pretty much following a backward clock, so there is some logic remaining. But not much.

(Mercifully ending this wretched lesson) Figure C shows that the carbon atom after #6, like #10a, makes no sense. Instead of being called #7, it's 6a (blue). Why? Once again, don't ask. A degree of sanity returns after this. Carbon #7 shows up next on the clock dial (4:00) and is followed by 8 and then 9. This is where the "delta-8" comes from. Greek letters are used to describe the position of double bonds (yellow line). The same holds true for dietary supplements, for example, omega-6 or omega-3 fish oils. Delta-8 means that the double bond exists between carbon atoms 8 and 9. The delta part is beyond the scope of this article. Be thankful for this.

And, if this wasn't sufficiently horrifying to have you opening up Amazon to order Final Exit, it can be worse. There is a 69-page document put out by the WHO titled "Isomers of THC." If you're looking for a little light reading this is as good as it gets. Take a look at this especially enthralling passage:

Ah, chemistry. Source: WHO, Isomers of THC

Seriously, who cares?

Both marijuana users and law enforcement care, otherwise I would not have dragged you through this hideous exercise. The position of that double bond determines both the pharmacological properties and legality of the chemical. The chemical properties of delta-8 and delta-9 THC (the "normal" THC in marijuana) are nearly identical, as are their chemical structures. The only difference in structure is the position of the double bond (yellow).

Pharmacology

As you'd expect, when two molecules are so similar they act similarly on the receptors in the brain. This is largely true, although there are subtle differences between the two. Delta-8 has a similar psychotropic profile to THC but is thought to be less potent. Relatively little is known about this drug because it arrived on the scene only recently and because cannabis and CBD oil contain only trace amounts of the chemical, so there wasn't enough around to isolate and study until an unnamed chemist figured out how to make it.  

Chemistry to the "rescue"

Two years ago I wrote about the chemical difference between CBD and THC – one chemical bond – and whether it was feasible to use CBD as a source for THC. (It isn't – the reaction that was used gave a mess (a complex mixture containing many impurities). 

HPLC trace of psychoactive substances formed by reacting CBD with dilute acid. There are at least four impurities present. Source: Cannabis and Cannabinoid Research Volume 1.1, 2016 DOI: 10.1089/can.2015.0004

But the chemist found that a different set of conditions enabled CBD could be converted not to THC, but to delta-8 THC, which spawned a cottage industry in the stuff (3). This chemistry is explained on the subtly named site Hempvada. Why do I think that their annual board of directors meeting looks something like this?

Hempvada BOD meeting? Photo: Flickr

A quick visit to the Hempvada site shows (unsurprisingly) that they are peddling CBD products. With a flair! Here are some of them:

• CBD Sunrocks 65%
• Flavored CBD Oil Tincture
• Santa Maria CBD Hemp Flower
• CBD Beard Oil
• Sour CBD Gummies
• CBD Energy Shots and CBD Oil Bundle
• CBD Sea Salt Scrub, Bath Bombs, and PM Facial Moisturizer Bundle (Seriously?)

Legal matters

Delta-8 was synthesized because it was previously "unknown" and therefore (possibly) legal. Or maybe it isn't. This depends on where you are and how drug laws are interpreted. It's a complicated mess. I haven't the bandwidth (or intellect) to go into the myriad of often contradictory laws governing the use of marijuana and its chemicals, but Jon Jackson writing for Newsweek and Bill Weinberg on the Project THC site do a very nice job of explaining this complex topic. 

Signing off

For all both of you who have made it through TCDHFH^® as well as the rest of this somnorific article, congratulations! Most humans would have taken one look at the nomenclature section alone and hastily switched over to reading prescription drug inserts. Feel free to reward yourself. Perhaps chow down on some pot brownies. Just keep in mind that what you're getting might not be so pure.

An HPLC trace of an extract of cannabis brownies. The damn things have more chemicals in them than the Gowanus Canal. Source: Sigma-Aldrich

NOTES:

(1) Synthetic organic chemistry is the science of converting one substance to another by the use of known reactions. It is the basis of much of drug discovery.

(2) I wasn't kidding. All of the following are legitimate names for delta-9 THC. There are 136 of them. Is it any wonder that chemists are thought of as some yet-to-be-defined, but aberrant species?

1. (-)-δ9-trans-Tetrahydrocannabinol
2. Δ9-Tetrahydrocannabinol
3. Δ9--THC
4. (-)-trans-δ9-Tetrahydrocannabinol
5. (-)-trans-δ9-THC
6. (-)-δ 9-Tetrahydrocannabinol
7. (-)-δ9-Tetrahydrocannabinol
8. (-)-δ9-Tetrahydrocannabinol
9. (-)-δ9-THC
10. (-)-δ9-trans-Tetrahydrocannabinol
11. (6aR,10aR)-6,6,9-Trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol [ACD/IUPAC Name]
12. (6aR,10aR)-6,6,9-Trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol [German] [ACD/IUPAC Name]
13. (6aR,10aR)-6,6,9-Triméthyl-3-pentyl-6a,7,8,10a-tétrahydro-6H-benzo[c]chromén-1-ol [French] [ACD/IUPAC Name]
14. 1972-08-3 [
15. 625-153-6 
16. 6H-Dibenzo(b,d)pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-, (6aR-trans)-
17. 6H-Dibenzo[b,d]pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-, (6aR,10aR)- [ACD/Index Name]
18. 6H-Dibenzo[b,d]pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-, (6aR-trans)-
19. Dronabinol 
20. Dronabinolum [Latin]
21. Δ9-THC
22. Marinol [Trade name]
23. Marinol (TN)
24. MFCD00083207 [MDL number]
25. Tetrahydrocannabinol [Wiki]
26. δ(9)-Tetrahydrocannabinol
27. δ1-Tetrahydrocannabinol
28. δ1-THC
29. δ-9-TETRAHYDROCANNABINOL
30. δ9-THC
31. δ9-THC
32. (-)- δ 9-Tetrahydrocannabinol
33. (-)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol
34. (-)-3,4-trans-δ1-Tetrahydrocannabinol
35. (-)-trans-δ 1-Tetrahydrocannabinol
36. (-)-trans-δ 9-Tetrahydrocannabinol
37. (-)-trans-δ 9-THC
38. (-)-trans-δ1-Tetrahydrocannabinol
39. (-)-trans-δ9-Tetrahydrocannabinol
40. (-)-δ 1-Tetrahydrocannabinol
41. (-)-δ 9-Tetrahydrocannabinol (δ9-THC) 100 µg/mL in Methanol
42. (-)-δ 9-Tetrahydrocannabinol (δ9-THC) 1000 µg/mL in Methanol
43. (-)-δ 9-THC
44. (-)-δ 9-trans-Tetrahydrocannabinol
45. (-)-δ(sup 1)-3,4-trans-Tetrahydrocannabinol
46. (-)-δ(sup9)-trans-Tetrahydrocannabinol
47. (-)-δ1-Tetrahydrocannabinol
48. (-)-δ1-Tetrahydrocannabinol
49. (-)-δ9-(trans)-Tetrahydrocannabinol
50. (-)-δ9-Tetrahydrocannabinol solution
51. (10R,10aR)-6,6,9-Trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol
52. (6aR,10aR)-3-amyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol
53. (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol
54. (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6H,6aH,7H,8H,10aH-benzo[c]isochromen-1-ol
55. (6aR,10aR)-6a,7,8,10a-Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1-ol
56. (6aR,10aR)-6a,7,8,10a-Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol
57. (6aR-trans)-6a,7,8,10a-Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1-ol
58. (L)-δ 1-Tetrahydrocannabinol
59. (l)-δ(sup 1)-Tetrahydrocannabinol
60. (l)-δ1-Tetrahydrocannabinol
61. (L)-δ1-Tetrahydrocannabinol
62. 1-trans-δ 9-Tetrahydrocannabinol
63. 1-trans-δ(sup 9)-Tetrahydrocannabinol
64. 1-trans-δ(sup9)-tetrahydrocannabinol
65. 1-trans-δ(sup9)-tetrahydrocannabinol
66. 1-trans-δ9-Tetrahydrocannabinol
67. 1-TRANS-δ-9-TETRAHYDROCANNABINOL
68. 3-Pentyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydro-6H-dibenzo(b,d)pyran-1-ol
69. 6,6,9-Trimethyl-3-pentyl-7,8,9,10-tetrahydro-6H-dibenzo(b,d)pyran-1-ol
70. 6,6,9-Trimethyl-3-pentyl-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyran-1-ol
71. 6aR,7,8,10aR-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol
72. 6H-Dibenzo(b,d)pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-, (6aR,10aR)-
73. 6H-Dibenzo(b,d)pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-, trans-
74. 6H-Dibenzo[b, d]pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-
75. 6H-Dibenzo[b, d]pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-, (6aR-trans)-
76. 6H-Dibenzo[b, d]pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-, trans-
77. 6H-Dibenzo[b,d]pyran-1-ol, 6a,7,8, 10a-tetrahydro-6,6,9-trimethyl-3-pentyl-
78. 6H-Dibenzo[b,d]pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6, 9-trimethyl-3-pentyl-, (6aR-trans)-
79. 6H-Dibenzo[b,d]pyran-1-ol, 6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-, trans-
80. 81586-39-2 [RN]
81. Cannabinol, 1-trans-δ(sup 9)-tetrahydro-
82. Cannabinol, 1-trans-δ(sup9)-tetrahydro-
83. Cannabinol, δ1-tetrahydro-
84. Cannabinol, δ1-tetrahydro-
85. Deltanyne
86. Exocyclic δ (9)(11)-Tetrahydrocannabiol
87. https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:66964
88. Δ9-THC (CRM)
89. Δ9-THC-d3 (CRM)
90. Δ9-THC-d9 (exempt preparation)
91. L-trans-δ 9-Tetrahydrocannabinol
92. L-trans-δ9-Tetrahydrocannabinol
93. L-trans-δ9-Tetrahydrocannabinol
94. L-δ 1-trans-Tetrahydrocannabinol
95. L-δ1-Tetrahydrocannabinol
96. l-δ1-trans-Tetrahydrocannabinol
97. L-δ1-trans-Tetrahydrocannabinol
98. Marinol®
99. Maxepa
100. Primolut
101. Syndros
102. Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1-ol
103. Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-ol
104. Tetrahydrocannabinol δ9
105. Tetranabinex
106. THC
107. trans-6a,7,8,10a-Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo(b,d)pyran-1-ol
108. trans-δ (-)-9-Tetrahydrocannabinol
109. trans-δ 9-Tetrahydrocannabinol
110. trans-δ9-Tetrahydrocannabinol
111. trans-δ9-Tetrahydrocannabinol
112. δ 1-Tetrahydrocannabinol
113. δ 1-THC
114. δ 9-Tetrahydrocannabinol
115. δ 9-THC
116. δ 9-trans-Tetrahydrocannabinol
117. δ(1)-Tetrahydrocannabinol
118. δ(9)-Tetrahydrocannibinol
119. δ(9)-THC
120. δ(sup 1)-Tetrahydrocannabinol
121. δ(sup 1)-thc
122. δ(sup 9)-tetrahydrocannabinol
123. δ(sup 9)-thc
124. δ(sup9)-THC
125. δ1-Tetrahydrocannabinol
126. δ1-Tetrahydrocannabinol (VAN)
127. δ1-THC
128. δ9-Tetrahydrocannabinol
129. δ9-Tetrahydrocannabinol
130. Δ9-tetrahydrocannabinol
131. δ9-Tetrahydrocannabinol (VAN)
132. δ-9-THC
133. δ-9-THC
134. Δ9-THC
135. δ9-trans-Tetrahydrocannabinol
136. δ9-trans-Tetrahydrocannabinol

(3) Chicago Sun Times: "An unregulated, weed-like drug dubbed ‘CBD on crack’ has spiked in popularity. Now the legal pot industry is calling for a crackdown."