A5: The tags "9(R)" and "9(S)" denote the particular chirality (stereochemistry) at the molecule's ninth carbon position. According to CIP guidelines, cannabinoids such as HHC, HHCP, and others feature one or more chiral centers, which are carbon atoms with substituents organized in two non-superimposable mirror-image configurations. These centers are represented by the letters R (rectus, Latin for right) or S (sinister, left). The carbon that corresponds to the 9-position in HHC/HHCP may be in the R or S configuration. In THC, this carbon was a component of the double bond, but following hydrogenation, it becomes a chiral center in HHC. Since the potencies of the various isomers vary, this is significant. The 9R isomer, which is often more physiologically active and conforms to THC's natural structure, is occasionally referred to as "alpha" in older literature.
Studies on HHC and HHCP, for instance, revealed that 9R-HHC is around 10× more effective at CB1 than 9S-HHC.
Likewise, 9R-HHCP has more potency than 9S. Therefore, "9(R)-HHCP" indicates that the product or topic of discussion is related to that particular enantiomer. Since hydrogenating THC produces two epimers, many HHC syntheses result in a combination of 9R and 9S. One may be primarily obtained by selective synthesis or purification. The degree to which the molecule fits into the CB1 receptor may be greatly impacted by the "R" and "S." When converted to HHC, natural Δ9-THC matches the 9R structure. Thus, 9S is much less active than 9R, which is similar to the naturally active version. Practically speaking, a product that has been enhanced with 9R-HHCP will be more robust. Chemists and knowledgeable customers may better understand stereochemical purity thanks to the labeling. Therefore, "9(R)" and "9(S)" simply indicate the three-dimensional orientation at that carbon; the S is the mirror image, while the R isomer interacts with enzymes and receptors in a particular orientation and spins plane-polarized light in a certain direction. The "glove" (receptor) will suit one hand better than the other, much like left-hand against right-hand. Thus, the more active enantiomer is 9(R), whereas the less active is 9(S). Q6: Can THCV have the same effects as THC and is it really psychoactive?
A6: The psychoactivity of THCV differs significantly from that of THC and is dose-dependent. THCV is not very psychoactive at low dosages (usually less than 10 mg); in fact, it may even inhibit some of THC's effects instead of producing a high. At these dosages, users often report only mild side effects like appetite suppression or a sensation of clarity rather than drunkenness. However, THCV might provide a slight high at greater dosages (20–30 mg and beyond). Compared to a similar THC high, the THCV high is often characterized as being lighter, more energetic, and shorter-lasting.
It usually doesn't produce extreme euphoria or couch-lock, but rather a fleeting intellectual buzz that sometimes comes with a wave of alertness or mental clarity. For instance, a 30 mg dosage of THCV may provide a little mood boost and head rush, but it typically wears off in two to three hours, which is quicker than THC. Some refer to this as a "functional high."
Additionally, it is said to be less anxiogenic, meaning that users often do not experience the paranoia that THC may at comparable dosages. But, milligram for milligram, THCV is not nearly as potent as THC. Usually, a far higher concentration of THCV is required to get close to the potency of a regular THC dosage. One human investigation found that 10 mg of THCV by itself had no discernible psychotropic effects.
Any "high" only happens at larger dosages, which are often not seen outside of pure goods. The THCV concentration in natural cannabis is often too low to produce a high, while it may somewhat alter the THC high (making it shorter or sharper). If someone intentionally consumes a large amount of refined form or concentrates, they will notice the effects. The basic lesson is that although THCV won't really make you high when used normally (and may even prevent a THC high), it may have a slight, transient psychoactive impact when taken in excessive dosages. Although it interacts with brain receptors and is psychoactive pharmacologically, it is not potently intoxicating until taken in large quantities. Q7: Are these novel cannabinoids, such as THCP, HHCP, and others, synthetic or natural?
A7: While HHCP, HHCPO, and HHCV are semi-synthetic and chemically modified from natural cannabinoids, THCP and THCV are naturally occurring cannabinoids that are present in Cannabis sativa (albeit in very minute quantities). To dissect it:
In 2019, tetrahydrocannabiphorol, or THCP, was first separated from a cannabis plant.
Though only in small amounts in some strains, it does exist naturally.
Due to the impracticability of obtaining the little natural quantity from plants, THCP is often generated chemically for commercial usage (e.g., from CBD or Δ9-THC derived from hemp). Therefore, even if THCP is found in nature, the substance you purchase was probably made in a lab using a hemp precursor.
Cannabis also naturally contains THCV (tetrahydrocannabivarin), with some African landrace strains having as much as 1% THCV.
It may be synthesized from CBD by a multi-step synthesis or extracted from those plants. However, it is unquestionably a phytocannabinoid that is produced by plants via their regular biosynthesis routes (it begins with divarinic acid rather than olivetolic acid, but it shares the same mechanism as THC). THCV is now being bred into several hemp strains.
Hexahydrocannabiphorol, or HHCP, is not found in nature. It is THCP's hydrogenated homologue.
It was initially created, according to reports, by Roger Adams in trials in the middle of the 20th century. More recently, it was put on the market by hydrogenating THCP, which most likely originated from hemp CBD. Therefore, HHCP is a synthetic cannabinoid, even if it has many similarities with natural ones. Because it is often generated from a natural starting material (such as converting CBD → Δ8-THCP → hydrogenate to HHCP), it is "semi-synthetic." HHCP cannot be directly biosynthesised by any cannabis plant.
Hexahydrocannabiphorol acetate, or HHCPO, is unquestionably synthetic. It is HHCP's acetate ester.
Nothing like that occurs in the plant; an acetyl group must be chemically added to HHCP. It is thus a synthetic derivative, just as heroin is an acetylated version of morphine.
Hexahydrocannabivarin, or HHCV, is THCV's hydrogenated counterpart.
Naturally, plants stop at THCV and do not make HHCV. Thus, THCV is chemically hydrogenated to produce HHCV (this process was also carried out by Roger Adams in the 1940s). Therefore, HHCV is a semi-synthetic molecule derived from natural THCV or another precursor and is not present in raw cannabis.
In conclusion, HHCP, HHCPO, and HHCV are synthetic derivatives that don't occur naturally and must undergo chemical processes to create, whereas THCV and THCP are naturally occurring phytocannabinoids (although usually in trace amounts). To meet legal requirements, all of them may be and often are produced using cannabinoids derived from hemp, such as CBD (hemp as feedstock). Be aware that some of them (THCV, THCP) may be derived from uncommon cannabis strains or, more likely, manufactured from hemp ingredients, while others (HHCP, etc.) are unquestionably synthetic due to their lack of natural occurrence. Though their creation is evidence of sophisticated cannabinoid chemistry, each of these isomers and analogs attempts to replicate or improve features of natural cannabinoids.
Q8: How do these cannabinoids' legal statuses relate in the US and abroad?
A8: Many of these cannabinoids are available in the United States as hemp derivatives, which is a gray area created by the 2018 Farm Bill. According to federal law, substances like HHCP, THCP, THCV, etc. are not specifically prohibited as long as the finished product has less than 0.3% Δ9-THC.
It is unclear, however, whether the DEA would see any of them as analogs of Schedule I narcotics, particularly those that function similarly to THC. State laws, however, differ greatly. In general:
States that have prohibited Delta-8 THC and similar intoxicants generated from hemp, such as Alaska, Idaho, Colorado, New York, etc., often have wide language prohibitions against HHCP, HHC, THC-O, THCP, etc.
States like Texas, Florida, and others that support hemp or haven't changed their laws permit the over-the-counter sale of these cannabinoids. THCV is permitted in more states since it is less intoxicating; as of 2024, it is supposedly authorized in 41 states.
While HHCP and THCP (very intoxicated) are prohibited in many jurisdictions, they are sometimes grouped together with Delta-8. Since regulations often include derivatives as well, HHCPO most certainly falls anywhere HHCP is prohibited. Since HHCV hasn't been singled out, it could go unnoticed while others are prohibited, but if a law states that "all hydrogenated derivatives of THC," then HHCV would also be included.
Legality is thus patchwork in the US. For instance, Colorado does not now permit certain hemp cannabinoids (except from in goods made with a license), whereas California does. Always review the most current laws in your state.
Internationally, the majority of nations consider anything that functions similarly to THC to be unlawful. Canada: Only authorized cannabis producers are permitted to sell cannabinoids, and they do not presently provide HHCP or THCP, which the law considers to be legal substitutes for THC. Europe: Cannabinoids are generally prohibited by EU and UK legislation outside of medicinal applications; for example, HHCP and its novel analogs have recently been outright prohibited in France and a few other countries.
In 2023, Japan outlawed HHCP and THCP analogs.
In summary, unless you live in a country with a legal cannabis market and the product is within that regulated framework, it is typically illegal to possess or sell these novel cannabinoids outside of the US. Even in those cases, the majority of these analogs are not yet available in regulated markets, with the exception of THCV in certain medical strains. Some nations may not have up-to-date legislation, so someone may claim that it's lawful, but it's dangerous since authorities or customs could perceive them as restricted narcotics. For instance, it may be claimed that THCV is not specifically scheduled, but because of its structural similarities to THC, it is considered similarly in many jurisdictions. Switzerland demonstrated the trend by aggressively banning THCP and comparable substances. In summary:
USA: State-dependent legality but federally unscheduled; many of them are supplied online when permitted.
International: Unless there is a clear carve-out, which is now uncommon, it is generally regarded as unlawful (Schedule I equivalent) by default. In most nations, it's fair to presume that these are restricted drugs since, even if regulations aren't up to date, enforcement will probably be unfriendly if found. The conservative position is that only CBD (and sometimes delta-9 THC in controlled situations) has any legal acceptability worldwide, whereas these innovative ones do not yet. However, you should always double-check local restrictions.
Q9: Are there any recognized hazards or long-term adverse effects associated with using these cannabinoids consistently?
A9: Based on our knowledge of THC and similar substances, we may draw the following conclusions concerning the long-term usage of these particular new cannabinoids:
Dependency and tolerance: Due to receptor downregulation, prolonged use of potent CB1 agonists, such as HHCP or THCP, is likely to cause tolerance, which requires greater dosages to have the same effect. Similar to high-THC cannabis, it is also possible to develop a habit that results in minor withdrawal symptoms including irritation and difficulty sleeping. Although no long-term research has been conducted, HHCP/THCP may cause tolerance more quickly since it hits CB1 much more strongly.
Effects on cognition or mental health: Long-term heavy use of high-potency cannabinoids may have dangers similar to long-term high-THC use, which might impair memory, cognitive function, or exacerbate underlying anxiety or psychotic tendencies. For example, frequent use of potent THC has been associated with certain cognitive impairments and a higher likelihood of psychotic symptoms in susceptible individuals. Although we don't have any case studies, it's possible that a comparable or higher risk may arise if someone were taking large dosages of THCP on a regular basis. However, because of their lower psychoactivity, THCV and HHCV are less likely to produce these effects (in fact, THCV may mitigate some of the negative effects of THC when used in combination).
Physical well-being: Cannabinoids don't readily harm organs and are typically well tolerated. Since there is currently no proof, we do not anticipate that cannabis analogs would cause liver damage. One possible concern to the cardiovascular system is that daily excessive use of powerful CB1 agonists may cause abrupt increases in blood pressure and heart rate, which over time may put stress on the heart in vulnerable people. Although there are no research specifically on HHCP/THCP, long-term cannabis usage has been linked to certain cardiovascular consequences, albeit the evidence is conflicting.
Social and psychological: Like any strong psychedelic, prolonged excessive usage may cause psychological dependency that affects day-to-day functioning or motivation problems. As with very powerful cannabis, a person's productivity or social interactions may be negatively impacted if they regularly use HHCP or THCP to become very high. Thus, usage poses a lifetime danger.
Particular worries: HHCPO's long-term danger is mostly related to its usage (we spoke about vaping problems and the potential for long-term lung damage). There hasn't been much research done on the long-term use of acetates like HHCPO; they probably get metabolized well, but inhalation is still a concern.
Although it's theoretical, long-term usage of THCV may be safe or even advantageous (if it aids in glucose or weight regulation). We would want to make sure that extended CB1 antagonistic effects don't result in mental adverse effects. Some persons developed depression as a result of chronic CB1 blocking (such as rimonabant); THCV is not as potent, but it would be prudent to take it on a frequent basis to check mood over the long run.
In conclusion, the well-known long-term consequences of cannabis (tolerance, potential dependence, effects on mental health in some people, etc.) probably also apply to these. Since these drugs are relatively new, anybody who uses them for extended periods of time is in somewhat unknown terrain. They should exercise caution, pay attention to their body and mind, and maybe cycle their usage to avoid developing a significant tolerance. It is advised to handle them with the same consideration as high-THC cannabis: moderate usage is likely to carry a tolerable risk, but heavy, long-term use may result in adverse effects that are typical of strong cannabis (and maybe more pronounced given increased potency). It's advised to err on the side of moderation when consuming these cannabinoids over an extended period of time until research catches up.
Q10: Do these cannabinoids have any noteworthy pharmacological interactions, such as with prescription drugs?
A10: There are many ways that cannabinoids may interact with other medications, including via metabolic (liver enzyme) interactions or by having additive effects on the cardiovascular or central nervous systems. Although there is a dearth of particular study on the interactions of these novel cannabinoids, we may deduce from the interactions between THC and CBD:
Metabolic interactions: Cytochrome P450 enzymes, particularly CYP3A4 and CYP2C9, metabolize a variety of cannabinoids, such as THC, CBD, and others. The same enzymes are probably used by THCP, HHCP, and others for metabolism. Therefore, there may be competition or inhibition if a person is taking a medicine that is likewise processed by these enzymes. For instance, CYP3A4 and CYP2C19 are known to be strongly inhibited by CBD. Some enzymes are moderately induced over time by THC. Although the precise effects of THCP and HHCP on enzymes are unknown, their structural resemblance to THC suggests that they may inhibit CYP2C9 or CYP3A4. Medication that depends on certain enzymes, such as some blood thinners, anti-seizure drugs, or even statins or SSRIs, may become more prevalent as a result. On the other hand, medications that stimulate certain enzymes, such as rifampicin or St. John's Wort, may lower levels of cannabinoids. It's hypothetical until research is done, however using them with sensitive medications should be done with caution.
Additive CNS depression: There is a chance of increased drowsiness or impairment if you combine strong cannabis with other drugs that depress the central nervous system, such as alcohol, opioids, benzodiazepines, etc. For example, combining HHCP or THCP with alcohol may increase vertigo, impair coordination, or increase the chance of blacking out. There is a pharmacodynamic interaction rather than a chemical one. In a similar vein, combining with other psychoactives may unexpectedly increase anxiety or alter heart rate.
Heart rate/BP: Although it is not a common combination, it is theoretically possible that taking stimulants like Adderall together with something like THCP, which increases heart rate, might place additional strain on the cardiovascular system. Alternatively, a large dosage of THCP may partly counteract a beta-blocker for blood pressure by increasing heart rate.
CBD interaction: To lessen the effects, several products combine CBD with these. According to some research, CBD may actually increase the half-life of THC by preventing its metabolism. Because CBD is a potent enzyme modulator, its presence may potentially delay or change the metabolism of THCP/HHCP. That can indicate a somewhat altered impact profile or a longer effect. Not a very risky encounter, but noteworthy.
Blood thinners (such as warfarin): Due of their competition for metabolism, THC and CBD may raise warfarin levels. Regular use of a cannabis may cause an increase in INR. These novel cannabinoids may act in a similar manner.
CBD is known to interact with anti-seizure drugs, including clobazam, by increasing their levels. Less research has been done on these others; large doses of THCV may also alter enzymes. It's advisable to use caution in the absence of hard evidence.
Sedatives/anesthetics: If a person is taking these cannabinoids and has surgery that requires anesthesia, the combined effects on heart rate or central nervous system may affect the dosage of anesthesia (although heavy daily users may require adjustments to anesthesia due to tolerance or interactions; occasional users are usually fine).
In conclusion, it is safe to infer that HHCP, HHCPO, THCP, and other cannabinoids function similarly to other cannabinoids, primarily via metabolic interactions via CYP450 and additive effects with medications that produce drowsiness or influence blood pressure or heart rate, even if we do not have clear interaction charts for them. Before using these cannabinoids, it is advisable to speak with a healthcare provider if you are using any critical medicines, such as blood thinners, antiseizure medications, or heart medications. Additionally, unless you are certain of your response, do not combine them with alcohol or strong sedatives. As a general guideline, because our systems probably react to them similarly, treat them the same way you would THC or potent cannabis.
Q11: Are there pictures or chemical diagrams that show these variations in cannabinoids?
A11: In agreement. We have included structural formula pictures for HHCP, HHCPO, HHCV, and THCP in the thorough study above. The main distinctions between each structure—such as side chain lengths or additional functional groups—are highlighted. For instance, the saturated ring and heptyl side chain are visible in the HHCP structure picture, but the HHCV image
shows the shorter side chain of propyl. These illustrations aid in comprehending the differences between a molecule such as THCV (propyl chain), THC (pentyl), and THCP (heptyl). Although I am unable to illustrate in language here, the photographs are included for reference in the article above. Regarding accessibility, the article displays the structures of THCP and other substances that have been disclosed in scientific literature. Those figures or sources such as Wikipedia or scientific papers, which often include 2D structural diagrams, may be consulted by anybody interested in the chemical specifics. The graphics depict the acetyl group linked to each incremental alteration, such as the "-O-acetate" in HHCPO. These pictures are named appropriately in the text and were added to help clarify the conversation. The 2D pictures in this article should be enough for a comparative understanding, but if further visualization is required, one might additionally see the 3D JSmol offered in certain sources or utilize 3D molecular modeling tools.
The cutting edge of cannabis research is represented by the cannabinoids HHCP, HHCPO, THCP, Δ8-THCP, HHCV, and THCV, which deepen our knowledge of how even minor chemical changes may significantly impact pharmacological characteristics. Although both THCP and THCV are found in nature, their remarkable receptor affinities and unique effects were only recently discovered. THCP's ultra-potency (binding CB1 approximately 33 times stronger than THC) and THCV's distinct antagonist-to-agonist dose-dependent behavior (suppressing appetite and psychoactivity at low doses, possibly aiding metabolic health) Hydrogenated analogs HHCP and HHCV show how double bond saturation may improve stability and alter psychoactivity; HHCP is a potent, persistent psychoactive drug (EC
50 ~44 nM at CB1).
However, HHCV is relatively modestly active, providing a potential window for treatment without intoxication. The development of HHCPO (HHCP-O-acetate) highlights the potential to further modify cannabinoids for prodrug effects, although at the expense of similar safety issues to those shown with THC-O. Mechanistically speaking, these cannabinoids support the idea that CB1/CB2 receptor interactions play a key role in determining effects: While shorter alkyl chains (THCV, HHCV) or additional functional groups (acetates) alter effectiveness and bioavailability, sometimes turning drugs into receptor blocks rather than activators, longer alkyl chains (THCP, HHCP) significantly increase CB1 agonism, producing higher psychotropic effects. According to research, their safety profiles are consistent with established cannabinoid pharmacology; they are typically low in acute toxicity but do carry certain dangers. Psychoactive substances (HHCP, THCP) have the capacity to produce strong central nervous system effects, as well as tolerance, acute anxiety, and tachycardia in the event of an overdose. Extensive longterm trials are required, however less psychoactive ones (THCV, HHCV) show promise for positive outcomes (weight management, anti-inflammatory) with few adverse effects. The range of adverse effects includes mild or even "positive" side effects including hunger suppression and improved attention (for low-dose THCV) as well as extreme euphoria and impairment (for HHCP/THCP at high dosages). Legally, we see a dynamic and uneven landscape: although most of these chemicals are still regulated similarly to THC worldwide, the US allows them under federal hemp legislation but confronts a patchwork of state restrictions, underscoring the disconnect between scientific innovation and legislative adaptation. These particular compounds demonstrate the ability to fine-tune cannabinoid effects in the developing field of cannabis science: we can now produce analogs that are more stronger, last longer, or, on the other hand, reverse the classical effects. Research and the creation of new treatments both benefit greatly from this. For example, THCP and HHCP enable researchers to examine what occurs when CB1 is overexerted, which may help map the capacity of the endocannabinoid system. THCV and HHCV provide models for drugs that might provide the anti-inflammatory or metabolic effects of cannabis without the high. THCV is already being considered as a potential therapy for diabetes and obesity. Although most people find early warning signs to be comforting (with the noteworthy exception of breathing acetates), prudence is necessary since broad human usage is still in its infancy. With various cannabinoids, particularly the stronger ones, microdosing has become popular as a way to get advantages (such as concentration or stress reduction) without becoming intoxicated; this is something that needs further official research. To sum up, these new cannabinoids expand the range of cannabis-derived instruments that researchers and consumers may use. While THCP and HHCP are strong alternatives in markets where strong psychoactive effects are desired (with the caveat of responsible use and legal compliance), compounds like THCV and HHCV, with their mild profiles, could be used sparingly as part of wellness or medical regimens (for energy, appetite control, or adjunct pain relief). Understanding pharmacokinetics, receptor selectivity, long-term effects, and the best dosage for each will be crucial in the future, as will thorough scientific and clinical assessment. This will guarantee that these cannabinoids' usefulness is optimized while lowering dangers. For instance, THCP's potency may be used to help patients who need high-dose THC effects in tiny amounts, while THCV's special activities can be used to create cannabinoid-based treatments for metabolic syndrome. Although cautious monitoring is still required, the available information points to a bright therapeutic future and a largely positive safety profile. All things considered, the emergence of HHCP, HHCPO, THCP, Δ8-THCP, HHCV, and THCV marks a new age in which cannabis research is progressing beyond the conventional paradigm of Delta-9 THC and CBD. Together, these substances' unique features provide a more complex picture of the pharmacological landscape of the endocannabinoid system and suggest potential uses in medicine and wellness. As of right now, they serve as evidence of the adaptability and strength of cannabis chemistry when directed by scientific knowledge, but their position will eventually be determined by ongoing study and practical input.
