THCP or THC-P is a recently discovered cannabinoid found in the cannabis plant, joining the ranks of THC and CBD. It has garnered broad attention in cannabinoid research due to its therapeutic potential. There are some wild claims of potency out there. What are the real facts and science behind THCP and how is it chemically synthesized?

What is THCP?

Did you know that almost 150 distinct cannabinoids have been isolated to date? Cannabis sativa is a plant that sparks debates. Some see it as a valuable source of medicine for conditions like glaucoma and epilepsy. But, at the same time, it’s the most commonly used illegal drug worldwide.

At a molecular level, THCP shares the basic framework common to cannabinoids such as tetrahydrocannabinol (THC / delta-9-THC) and cannabidiol (CBD). You can see the chemical structure in the figure.

What sets THCP apart is its heptyl side chain. Chemically speaking, this is a seven-carbon alkyl group with the chemical formula -C₇H₁₅. THC on the other hand bears a pentyl group (-C₅H₁₁). The length of this chain directly influences binding to the CB receptors (see below) and thus the cannabimimetic activity. This side chain is also called the pharmacophore due to its influence on biochemical activity.

THCP Flower Concentration

The concentration of THC-P in Cannabis Sativa is estimated to be 0.0023% to 0.0136% (0.02–0.14 mg/g) [1]. In comparison, normal THC occurs in up to 30%! These levels seem too low to trigger significant effects or subtherapeutic.

However, not only is THC-P a stronger CB binder than THC, but other phytochemicals may influence efficacy and experience of C. sativa use. Through a so-called entourage effect, there may be synergistic interactions with the major cannabinoids and other phytochemical components.

Due to the low natural concentration, THC-P is more conveniently (for research purposes) synthesized chemically.

How is THC-P Made? (Synthesis)

The organic chemistry behind THCP is actually simple. The starting material is a chiral allylic alcohol for the enantioselective synthesis. The hydroxy group can be substituted with an aromatic ring bearing the linear side chain. Under acidic conditions, we have first the allylic substitution and second an addition of a phenol group to the olefin.

The only issue in this very direct synthesis is the formation of olefin isomers. To get to the right configuration in THC-P, the intermediate (-)-trans-Δ⁸-THCP can be isomerized. This works through step-wise hydrochlorination and a surprisingly very selective elimination using potassium t-amylate as base.

THC-P Mechanism of Action

THC-P interacts with cannabinoid receptors CB1 and CB2 which are part of the so-called endocannabinoid system or ECS. The ECS is a complex network of receptors, endocannabinoids, and enzymes distributed throughout the body. It plays a crucial role in maintaining homeostasis which is the body’s self-regulation process.

Early research suggests that THC-P may have a higher affinity for CB1 receptors, which are predominantly found in the central nervous system. CB1 receptors play a key role in regulating neurotransmitter release, impacting various physiological functions such as mood, appetite, and pain perception.

The figure d) shows the binding very nicely. The yellow dashed line represents a pocket of hydrophobic amino acids where the linear alkyl side chains reside. Because the longer heptyl side chain has more contacts, it shouldn’t surprise you that THC-P had stronger binding compared to normal THC.

As you can see in a), THC-P has a >30-fold and >6-fold increased binding for the cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). The affinity value of 1.2 nM (nanomolar) is very strong on a “molecular” level!

However, the research is too immature to be able to say “how much more potent” it actually is. Nevertheless, preliminary evidence suggests that THC-P may modulate neurotransmitter release in a way that differentiates it from other cannabinoids. There are several areas of potential therapeutic application.

THC-P Effects: Appetite Regulation

One notable aspect of THC-P is its reported appetite-suppressant effects. We clearly need more research to understand the underlying mechanisms but this property raises the possibility of THC-P as a tool for weight management and addressing conditions related to overeating. A study conducted on rodents investigated the effects of THC-P on feeding behavior. The results suggested that THC-P administration led to a reduction in food intake, providing initial support for its appetite-modulating properties.

THC-P Mood Disorders and Anxiety

The interaction of THC-P with CB1 receptors, particularly in the brain, points to potential applications in mood disorders and anxiety management. The modulation of neurotransmitter release in key brain regions may offer a novel approach to addressing conditions characterized by mood imbalances. However, preclinical studies have so far only indicated the anxiolytic potential of cannabinoids in general, not THC-P specifically.

THCP Epilepsy

THC-P may hold promise for neurological conditions. Conditions such as epilepsy and neurodegenerative disorders might benefit from further investigation into THC-P’s effects on neuronal excitability and neuroinflammation. Preliminary data from animal studies has shown cannabinoids, including THC-P, to have anticonvulsant properties.

Is THCP Legal?

The legal status of THC-P varies by country. In the United States, THCP unlike THC is not specifically listed as a Controlled Substance federally. However, regulations vary by state or country. In the rest of the world, THCP is currently legal in Germany, for example. Other countries classify THC-P as a controlled substance. With the current dynamic regarding medical use of cannabis, shifts in legal stands and regulations are to be expected. We have discussed increasing interest on the public level on psychedelic compounds such as ibogaine or psilocybin/ psilocin.

Is THCP Safe?

Given the early days of THCP research, safety aspects, particularly in humans, are not clear. The psychotropic effects of THC-P could raise concerns, particularly regarding cognitive function and the potential for dependence. Long-term studies are essential to assess the safety profile and any adverse effects associated with THC-P use.

In addition, it will be key to establish standardized testing methods to validate high-quality material for research purposes. Standardization is essential for accurate dosing, reproducibility of results, and ensuring the reliability of research.

As THCP is present in only little amounts in C. sativa, THCP products on the market may have been produced synthetically and not have been tested for safety, purity, or potency. Thus, we discourage consumption of (any) supposedly safe drugs and medicines in absence of professional medical oversight and need.

Summary

THC-P, with its distinctive molecular structure and potential therapeutic applications, represents a promising avenue for cannabinoid research. As our understanding of its chemical properties and interactions with the endocannabinoid system deepens, the door opens to innovative approaches in medical science.

While challenges exist, the increasing scientific interest suggest that THC-P could play a significant role in the future of medicine. Responsible research, transparent communication, and thoughtful regulation are paramount in unlocking the full potential of THC-P, other cannabinoids and medicines at large.

Information for THCP

• J. Nat. Prod. 2021, 84, 2, 531 | (−)-trans-Δ⁹‑Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes
• Scientific Reports 2019, 9, 20335 | A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ⁹-tetrahydrocannabinol: Δ⁹-Tetrahydrocannabiphorol