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Subjective Effects
The recently published study by Pelgrim et al. strongly supports that THC elevates subjective experiences like “feeling high,” creates altered perception, and subjective feelings of euphoria/dysphoria [1]. These measurements, taken through Visual Analogue Scales (VAS), reached statistical significance, offering robust direct evidence for THC’s impact on human cognition and emotion.
Functional Connectivity
The researchers observed that THC affects the way two important areas of the brain communicate: the Salience Network and the Hippocampus-Midbrain-Striatum Network [1]. In simpler terms, THC acutely impacts the brain’s ability to focus on important or emotionally charged information. This aligns with previous research, further solidifying the findings [2,3].
Additionally, the researchers noticed some changes in a brain network often linked to mental health conditions like psychosis, although these findings were not definitive as the trendline failed to reach significance.
Genetic Modulation
The researchers discovered that individuals with a specific genotype of the catechol-O-methyltransferase (COMT) gene, a gene crucial for efficient degradation of dopamine, particularly those with the Met/Met variation, experienced heightened dysphoric reactions to THC. A similar trend was observed in these individuals concerning functional connectivity within the Hippocampus-Midbrain-Striatum Network, though it did not reach statistical significance.
*Figure 3 republished from original manuscript* Genotype-dependent increase in subjective feelings of dysphoria (N=51), measured using VAS (Visual Analogue Scales). A significant interaction effect of drug and genotype was found for experience of dysphoria after THC (F(2,48) = 6.30; p = 0.004). Individuals with a Met/Met genotype reported a significant increase in dysphoria after THC (t(18) = 3.01; p =.008), whereas Val allele carriers did not. (Val/Val N=14, Val/Met N=18), Met/Met N=19).
Editor’s Comments
In simpler terms, this study unequivocally shows that THC, the component in cannabis that makes you feel “high,” acutely alters how certain areas of the brain communicate with each other. These effects are even more pronounced in people with a specific genetic makeup. However, what you “feel” under the influence of THC doesn’t necessarily correlate with what’s happening inside your brain.
Broader Context and Emerging Importance
The findings contribute to the fast-growing body of research on the Endocannabinoid System (ECS) and its more extensive organizational framework, which is more appropriately referred to as the Master Homeostatic Regulatory System (MHRS). The results extend the current understanding by showing how THC affects key brain networks and how these effects are influenced by genetic factors like COMT genotypes.
Physiological Implications
The MHRS plays a critical role in maintaining the body’s internal balance or homeostasis. However, this new study shows that THC — the main psychoactive component in cannabis —can disrupt this delicate balance. This disruption is particularly evident in brain regions responsible for emotional and cognitive processing. People with a certain genetic makeup, specifically those with the COMT MET/MET variation, are more sensitive to these disruptive effects and predisposed to experiencing dysphoric effects from THC. This is particularly important for understanding the risk of mental health conditions like depression and schizophrenia, which are known to involve dopamine imbalances.
Neurobiological Importance
This study sheds new light on the role of the COMT enzyme, crucial for dopamine metabolism, in THC’s acute effects. The new observations strengthen the rationale for targeting the ECS to treat diseases related to dopamine. It also gives scientists new clues as to why THC, in some patients with Parkinson’s disease, can be very efficacious for symptom management.
Participant Diversity and Limitations
This study mainly included people who use cannabis occasionally. Future studies should consider including people who use cannabis more frequently and those from diverse backgrounds to make the findings more applicable to a wider audience.
Conclusion
This study strongly suggests that THC acutely changes the way key areas of the brain communicate and that genetics play a role in these effects. These findings are important for both the recreational and medical use of cannabis and open new avenues for research on its potential long-term effects on mental and dopaminergic health.
Stefan Broselid, Ph.D.
Editor-In-Chief, Aurea Care Medical Science Journal
References:
- Pelgrim TAD, Ramaekers JG, Wall MB, Freeman TP, Bossong MG. Acute effects of Δ9-tetrahydrocannabinol (THC) on resting state connectivity networks and impact of COMT genotype: A multi-site pharmacological fMRI study [published online ahead of print, 2023 Aug 12]. Drug Alcohol Depend. 2023;251:110925. doi:10.1016/j.drugalcdep.2023.110925
- van Hell HH, Bossong MG, Jager G, et al. Evidence for involvement of the insula in the psychotropic effects of THC in humans: a double-blind, randomized pharmacological MRI study. Int J Neuropsychopharmacol. 2011;14(10):1377-1388. doi:10.1017/S1461145711000526
- Bossong MG, van Hell HH, Schubart CD, et al. Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype. Eur Neuropsychopharmacol. 2019;29(6):766-776. doi:10.1016/j.euroneuro.2019.03.010