Table 1 THC-like cannabinoids in the recreational market: natural occurrence, manufacturing process, structure, methods used for analytical assessment, CAS registry number, in vitro evaluation of CB1R binding affinity (Ki) in relation to the Ki of the reference Δ9-THC and experienced effects after recreational use
From: An emerging trend in Novel Psychoactive Substances (NPSs): designer THC
Natural occurrence | Manufacturing process | Structurea | Analytical assessment | CAS RNb | CB1R affinity (Ki) (nM) (Ref.) | Reference Ki for Δ9-THC (nM) | Recreational effects |
|---|---|---|---|---|---|---|---|
Naturally occurring in traces (PNCs) | Semi-synthesis (SSPNCs) |
| GC-MS with derivatization (Nahar et al. 2020) HPLC-HRMS (Nahar et al. 2020) HPLC-DAD (SCLabs 2022; Inc. SAS 2023) HPLC-UV (Analytical 2021) | 23978-85-0 | 3100 (Zagzoog et al. 2020) | 50 | Vaping or dabbing are the recommend ways to consume them in progressively increasing doses (TheChronicBeaver 2021; Bortolazzo n.d.) The best experience in terms of “high” effects and taste is achieved by blending them with terpenes or cannabis (reddit.com. 2021) |
| HPLC-UV (Citti et al. 2020; –Song et al. 2022) HPLC-HRMS (Kiselak et al. 2020; Pellati et al. 2018) GC-MS (Sams 2022) | 5957-75-5 | 45 ± 12 (Martin et al. 1999) | 41 ± 1.7 | Milder psychoactive and side effects compared to Δ9-THC (Schmidt 2023) | ||
| NP-HPLC-UV (Williams et al. 2021) Chiral HPLC-UV (Umstead 2021) GC-MS (Ciolino et al. 2021) 2D-LC-MS/MS (Chan-Hosokawa et al. 2021) | 95543-62-7 (9R) 95588-87-7 (9S) | - | - | Uplifting and energizing effects (Schmidt 2023) Enhancement of motivation, creativity, and cognitive function (Schmidt 2023) Less potent than Δ8-THC (reddit.com. 2020) | ||
| NP-HPLC-UV (Williams et al. 2021) Chiral HPLC-UV (Umstead 2021) GC-MS (Ciolino et al. 2021) 2D-LC-MS/MS (Chan-Hosokawa et al. 2021) | 95720-01-7 (9R) 95720-02-8 (9S) | 5 ± 2 (Rosati et al. 2014) | 22 ± 13 | Milder effects than Δ9-THC (Schmidt 2022) Uplifting and energizing effects Heightened sense of mental clarity and focus without paranoia and anxiety (Schmidt 2022) | ||
| GC-MS, GC-FID, NMR, FT-IR (Friedrich-Fiechtl and Spiteller 1975; Kettenes-van den Bosch and Salemink 1977) HPLC-MS (Lewis et al. 2017) | 56154-60-0c | - | - | Supposed similar properties as Δ9-THC (Hewett 2022; What is 10-Oxo-Δ6a(10a)-tetrahydrocannabinol (OTHC)? 2023) | ||
| NP-HPLC-UV (Banijamali and Makriyannis 1987) RP-HPLC-UV (Krepich et al. 2020; Franklin and Wilcox 2019) RP-HPLC-DAD (Ciolino et al. 2021) | 27179-28-8 | (IC50) 334 (Compton et al. 1991) | (IC50) 218 | “Good spacey feeling” and slow reaction time, though keeping a clear head sensation (reddit.com. 2023) | ||
| 36557-05-8 | 0.37 (Zagzoog et al. 2022) | 35 | Quick onset and a strength close to THC, along with an accelerated heartbeat and racing thoughts (reddit.com. 2023) | |||
| GC-MS (Vree et al. 1972; Vree et al. 1973) HPLC-UV, NMR, TLC (Stothard et al. 2023) | 6692-85-9 (racemic) 36403-90-4 (9R) 36403-91-5 (9S) | 19 (Ujváry 2023) | 27 | Effects comparable to those of Δ9-THC (sedation and relaxation, euphoric high and a smooth, calming experiencel) and sporadic side effects like psychosis, uncontrolled tremors, etc. (reddit.com 2023; Schmidt 2023; reddit.com 2023). | ||
| 73648-83-6 (9R,10S) 60948-21-2 (9S,10R) | - | - | Effects similar to those of HHC itself, although a bit shorter in duration (reddit.com. 2023) | |||
| - | 2041284-40-4 | - | - | Not used as such but after decarboxylation into HHC | ||
| - | 60491-22-7 | - | - | Expected to have the same effects as Δ9-THC, but more reactive to liver metabolism (Jagannathan 2020) | ||
Synthesis (SPNCs) |
| HPLC-HRMS (Linciano et al. 2020a) | 60008-00-6 | 15 (Linciano et al. 2020a) | 41 | Effects either comparable or higher to those of Δ9-THC (Brandrup 2023; Future4200. 1807) Quick sensations of euphoria, mental energy and uplift, bodily relaxation and calmness (Brandrup 2023) | |
| HPLC-HRMS (Linciano et al. 2020b) | 36482-24-3 | - | - | The psychoactive effect lasts longer than that of Δ9-THC (reddit.com, 2023) | ||
| ELISA (Moody et al. 2022) HPLC-HRMS (Citti et al. 2019) | 54763-99-4 | 1.2 (Citti et al. 2019) | 40 | More potent than Δ9-THC Effects could last up to 24 h or more (reddit.com. 2022) | ||
| - | 1349000-38-9c | - | - | Fast onset and decrease of the effects (edibles) (TSM. 2023) | ||
| - | 1348837-48-8c | - | - | Vaping HHCH distillates gives a mild sensation, much lower than the corresponding THC hexyl counterpart THCH (reddit.com. 2023) HHCH edibles produce a high psychoactive effect (reddit.com. 2023) | ||
| GC-MS, NMR (EMCDDA. 2023) | 2891843-81-3c | - | - | Unprecedented euphoria, intense uplifting effects and mood boost (Schmidt 2023) | ||
Unnatural (NNCs) | Semi-synthesis (SSNNCs) |
| ELISA (Moody et al. 2022) DART-QToF, GC-MS, LC-MS/MS (Holt et al. 2022) | 23132-17-4 | - | - | Stronger and delayed effects with respect to Δ8-THC and Δ9-THC, sometimes with some psychedelic effects like increased time dilation, deeply internalized self-contemplation and complete focus on only one thing at a time (reddit.com. 2021) |
| DART-QToF, GC-MS and LC-MS/MS (Holt et al. 2022) | - | - | - | Effects 1.5 times higher than HHC (What is HHC-O? The Complete Guide 2022) Sedation and relaxation, removal of overwhelming thoughts, more relaxed sleep, blissfulness, openness to new sensations and ideas (binoid 2022; Heredia 2022) Later onset of the effects compared to other cannabinoids (reddit.com. 2023) Episodes of panic attacks after consuming edibles with a sort of chronic depressive mood lasting for a few weeks afterwards (reddit.com. 2023) | ||
| 36403-93-7 (8S,9R) 42793-11-3 (8R,9S) | - | - | Quicker onset of the effects compared to HHC but the physical and mental experience is basically the same (reddit.com. 2023) | |||
Synthesis (SNNCs) |
| GC/MS (DEA 2019) Quantisaldevice (Coulter et al. 2011) | 112830-95-2 | 0.23 ± 0.03 (Howlett et al. 1990) | 1.6 | Higher potency compared to Δ9-THC, high safety (reddit.com. 2023), and long-lasting effects (Bluelight 2018) Low doses provide the desired “high” effects in very short time, high doses can produce dissociative and psychedelic effects, and medium doses have good analgesic properties (Bluelight 2016) | |
| - | 2829292-82-0 | - | - | Longer lasting and more euphoric effects compared to THCP, but also a later onset (up to 30–45 min) (Bluelight 2023; Black et al. 2023) Euphoria, relaxation, intoxication, or drowsiness (Canatura 2023) Anxiety, drowsiness, dry mouth, red eyes, and paranoia (Black et al. 2023) | ||
| - | 2829292-83-1c | - | - | Strong and long-lasting effects, but slow onset of the effects (reddit.com. 2023; Thomas 2023) Relaxation, intense euphoria, pain relief, warm body vibrations, and creative inspiration (DottorCanapa 2023) | ||
| HPLC (reddit.com. 2023) | 2552798-63-5 | 8.5 ± 1.4 (Martin et al. 1999)d | 41 ± 1.7 | Effects higher than those of Δ9-THC, enhancement of good mood, hunger, sleepiness, etc. (GasDank 2022). | ||
| HPLC (SDPharmLabs 2022) | 2411462-90-1 (acetoacetate) | - | - | Mellowing, relaxing, euphoriant, and energizing sensations with possible side effects including anxiety, dry mouth, dry or red eyes, increased appetite, increased heart rate, memory loss, slightly declined cognitive function, and slowed reaction times (Ward 2024) |
