THCP: Understanding a Newly Discovered Cannabinoid

For decades, delta-9-tetrahydrocannabinol (THC) has been recognized as the primary psychoactive compound in cannabis. However, the 2019 discovery of tetrahydrocannabiphorol (THCP) by Italian researchers revealed that our understanding of cannabis chemistry remains incomplete. This article examines what current science reveals about THCP, the limitations of existing research, and what questions remain unanswered.

The Discovery and Chemical Structure

THCP was first identified in 2019 through advanced mass spectrometry and metabolomics analysis of the Italian medical cannabis variety FM2. The discovery was published in Scientific Reports, a peer-reviewed journal.

Structural Differences

The molecular structure of cannabinoids includes an alkyl side chaina series of carbon atoms that influences how the molecule interacts with receptors in the body. Key structural distinctions include:

• Delta-9-THC: Contains a five-carbon alkyl side chain (pentyl)
• THCP: Contains a seven-carbon alkyl side chain (heptyl)

This two-carbon difference may seem minor, but it has significant implications for receptor binding. Previous research has established that cannabinoids with longer side chains (up to seven carbons) demonstrate increased affinity for cannabinoid receptors, while those with shorter chains show reduced activity.

The Endocannabinoid System and Receptor Binding

To understand THCP’s potential effects, it’s essential to understand the endocannabinoid system (ECS), a complex cell-signaling network present in all mammals.

CB1 Receptors

CB1 receptors are predominantly found in the central nervous system and are responsible for mediating many of cannabis’s psychoactive effects. These receptors influence:

• Cognitive function and memory formation
• Pain perception
• Mood regulation
• Motor coordination
• Appetite and metabolism
• Sensory perception

Binding Affinity vs. Functional Potency

The 2019 study found that THCP exhibited approximately 33-fold greater binding affinity for CB1 receptors compared to THC in laboratory conditions. However, it’s crucial to distinguish between different measures of cannabinoid activity:

1. Binding affinity: How tightly a molecule attaches to a receptor
2. Functional potency: How effectively it activates the receptor to produce biological effects
3. Efficacy: The maximum response a compound can produce
4. Clinical effects: Real-world outcomes in human subjects

In laboratory studies using mouse models, THCP demonstrated activity at doses 5-10 times lower than THC for certain measured effects. However, these animal models may not directly translate to human experiences.

Current Research Limitations

Understanding THCP’s effects requires acknowledging significant gaps in current knowledge:

Limited Human Studies

As of now, there are no published clinical trials examining THCP’s effects in human subjects. All potency estimates derive from:

• In vitro (test tube) receptor binding assays
• Animal behavioral studies
• Computational molecular modeling

Unknown Pharmacokinetics

Critical questions remain unanswered regarding how THCP behaves in the human body:

• Absorption rates: How quickly is it absorbed through different routes of administration?
• Metabolism: How is it broken down by the liver and other organs?
• Half-life: How long does it remain active in the system?
• Bioavailability: What percentage of consumed THCP produces active effects?

Natural Occurrence and Concentration

THCP occurs naturally in cannabis, but typically at concentrations below 0.1% of total cannabinoid content far less than THC, which can comprise 15-30% in modern cultivars. This raises important questions:

• Does naturally occurring THCP contribute meaningfully to a strain’s overall effects?
• Do different cannabis varieties produce different amounts?
• What environmental or genetic factors influence THCP production?

Theoretical Effects and Safety Considerations

Based on its pharmacological profile, researchers hypothesize that THCP may produce:

Potential Effects

• More pronounced psychoactive effects at lower doses than THC
• Longer duration of action (due to stronger receptor binding)
• Enhanced effects on pain perception, appetite, and sedation
• Possible differences in subjective experience quality

Safety and Risk Factors

The enhanced potency suggested by binding studies raises several public health considerations:

1. Dose uncertainty: Without established dosing guidelines, users may unintentionally consume excessive amounts
2. Acute adverse effects: Stronger CB1 activation could increase risk of anxiety, paranoia, disorientation, or panic reactions
3. Impairment: Greater impact on coordination, reaction time, and cognitive function
4. Individual variability: Genetic differences in cannabinoid metabolism may cause unpredictable responses
5. Vulnerable populations: Potentially greater risks for individuals with mental health conditions, pregnant individuals, or adolescents

Regulatory and Legal Context

The legal status of THCP exists in a state of flux, complicated by several factors:

Federal Considerations

• The 2018 Farm Bill legalized hemp-derived cannabinoids containing less than 0.3% delta-9-THC
• THCP is not explicitly mentioned in the Controlled Substances Act
• The Federal Analogue Act could potentially classify THCP as a Schedule I substance due to structural similarity to THC, but enforcement remains unclear

State-Level Variation

States have adopted diverse approaches:

• Some explicitly regulate all “tetrahydrocannabinols” or “intoxicating cannabinoids”
• Others maintain restrictions only on specific compounds like delta-9-THC
• Several states have enacted total THC testing requirements that would include THCP
• Regulations continue to evolve as new cannabinoids emerge

Testing and Product Labeling

Unlike THC, standardized testing protocols for THCP are not yet widely established, creating challenges:

• Inconsistent product labeling
• Difficulty verifying claimed concentrations
• Potential for mislabeled or contaminated products
• Lack of regulatory oversight in many markets

The Broader Context: Minor Cannabinoids

THCP is one of over 100 identified cannabinoids, and its discovery highlights how much remains unknown about cannabis chemistry. Other recently discovered or studied minor cannabinoids include:

• THCB (tetrahydrocannabutol): Four-carbon side chain variant
• CBDP (cannabidiphorol): CBD analog with seven-carbon side chain
• THCJD: Nine-carbon side chain variant
• CBG (cannabigerol): Precursor molecule to THC and CBD

Each of these compounds may interact with the endocannabinoid system differently, and research into their individual and combined effects remains in early stages.

What This Means for Cannabis Understanding

The discovery of THCP carries several important implications:

Strain Variability Explained

Some cannabis varieties have historically been reported as producing stronger or qualitatively different effects than THC content alone would predict. THCP and other minor cannabinoids may partially explain these observations through:

• Additive effects with THC
• Synergistic interactions (the “entourage effect”)
• Different receptor activation patterns

Need for Comprehensive Testing

Traditional cannabis testing focuses primarily on THC and CBD. The existence of potent minor cannabinoids suggests that:

• Full cannabinoid profiles provide more complete information
• Potency cannot be assessed by THC content alone
• Consumer and patient education requires more nuanced understanding

Future Research Directions

Priority areas for future THCP research include:

1. Controlled human clinical trials establishing dose-response relationships
2. Comparative studies examining effects versus THC in matched doses
3. Long-term safety and toxicity assessments
4. Therapeutic potential investigations for specific conditions
5. Interactions with other cannabinoids and medications
6. Individual variation studies based on genetic and metabolic factors

Conclusion

THCP represents an important advancement in cannabis science, demonstrating that significant gaps remain in our understanding of this complex plant. While preliminary evidence suggests THCP may bind more strongly to cannabinoid receptors than THC, translating this finding to real-world human effects requires rigorous clinical research.

As with any newly identified compound, caution is warranted. The enhanced receptor affinity observed in laboratory studies suggests THCP could produce stronger effects than anticipated, particularly in products where it has been concentrated beyond natural levels.

For consumers, patients, researchers, and policymakers, THCP underscores the importance of:

• Evidence-based approaches to cannabinoid regulation
• Comprehensive product testing and transparent labeling
• Continued investment in cannabinoid research
• Recognition that cannabis science remains an evolving field

The story of THCP is far from complete. As research progresses and our understanding deepens, this cannabinoid will likely continue to reshape our knowledge of how cannabis interacts with human biology.

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References and Further Reading

For those interested in exploring the scientific literature on THCP:

• Citti, C., et al. (2019). “A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ9-tetrahydrocannabinol: Δ9-Tetrahydrocannabiphorol.” Scientific Reports, 9(1), 20335.
• Pertwee, R. G. (2008). “The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin.” British Journal of Pharmacology, 153(2), 199-215.

Lu, H. C., & Mackie, K. (2016). “An introduction to the endogenous cannabinoid system.” Biological Psychiatry, 79(7), 516-525.