While the thought of not getting high from smoking marijuana may cause some to break out in a cold sweat just thinking about it, it seems that there is a pretty important functional physiological reason why the body prevents us from getting high when exposed to particularly high doses of THC (the psychoactive component of cannabis which causes the high). Research carried out by Vallee and colleagues in 2014 found that the administration of THC to Wistar rats resulted in the production of a steroid which reduced the effects of THC.
The particular “buzzkill” responsible for inhibiting THC’s effects, including its high, is a steroid called pregnenolone, which is produced by the adrenal gland and is believed to be an immediate precursor to all other steroid hormones produced within the body. In fact, pregnenolone is already available as an over the counter medicine. It is sold as an anti-aging supplement as it is a precursor to steroid hormones like testosterone and estrogen, which naturally decline as we get older.
Before I discuss the experiment conducted by Vallee et al. that was published in January 2014, let’s have a look first at how cannabis interacts with our own biological system, and more specifically, the endocannabinoid system in our body. “Endo” is short for endogenous, which means that it originates within, or is produced naturally by our body. Cannabinoids are the chemical compounds contained in marijuana, with the most well-known being delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The human body produces cannabinoids, too, known as endocannabinoids, hence the name of the system which interacts with the cannabinoids produced by the cannabis plant.
THC is the psychoactive component of the cannabis plant and is the specific phytocannabinoid (cannabinoids produced naturally by the cannabis plant) which interacts with the cannabinoid receptor CB1 in the human body, which results in us getting high. (CB1 and CB2 are the two most researched cannabinoid receptors in the human body).
The endocannabinoid System is comprised of three main components:
- Cannabis receptors contained in the nervous system and throughout the body which bond with endocannabinoids and cannabinoids
- Enzymes which break down these endocannabinoids and cannabinoids in the body
While the endocannabinoid system is responsible for a number of different tasks throughout the body, its most important function is the role it plays in maintaining homeostasis (which it does along with other systems in the body, such as the endocrine and nervous system, organs, etc.). Homeostasis is the process by which the body maintains a balanced internal environment in response to external influences.
The endocannabinoid system contributes to homeostasis in the body by regulating a number of processes such as pain management, immunological responses, appetite, energy, mood, and memory function, to name a few. In simplistic terms, the endocannabinoid system strives to maintain homeostasis by using cannabinoids and cannabinoid receptors located throughout the body, in the immune system and the central and peripheral nervous systems. When the endocannabinoid system detects an imbalance in the body, it synthesizes new cannabinoids to restore homeostasis.
So What Could Prevent Us from Getting High After Smoking Weed?
A 2014 study (“Pregnenolone Can Protect the Brain from Cannabis Intoxication”), carried out by researchers predominantly based in the French National Institute of Health and Medical Research (INSERM), produced some fascinating findings. The research carried out by Vallee and colleagues involved administering drugs like cocaine, morphine, nicotine, alcohol, and THC to Wistar rats (rats bred specifically for biological and medical research).
The Wistar rats were given doses of THC at median doses of 3mg per kg of body weight. The administering of THC resulted in the activation of the CB1 receptors in the rats’ brains, which caused them to produce pregnenolone in response. Interestingly, the researchers found the same results when a high level of THC was later exposed to human cell lines.
What was most striking about the study was how much pregnenolone was produced in response to THC. While the other drugs used in the research (alcohol, morphine, nicotine, cocaine) resulted in approximately a 300% increase in pregnenolone, THC produced a whopping 1500% increase in pregnenolone (the highest increase in pregnenolone was 3000% above the level of the control Wistar rat).
The frontal region of the Wistar rats’ brains, including the prefrontal cortex, striatum, thalamus and nucleus accumbens, were the locations which showed the largest increase in pregnenolone production. These areas of the brain are involved in motor and rewards systems, with the latter being involved in motivation, desire, craving, positive rewards which involve pleasure, planning, personality expression, decision-making, consciousness, and sensation.
Vallee et al. concluded from their research that:
“The administration of the main active principle of Cannabis sativa (marijuana), ∆9-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC.”
In essence, the administration of THC causes the body to produce the steroid pregnenolone, which reduces the effects of THC, including the high that THC produces.
Final Thoughts on Not Getting High after Smoking Weed
Just as the endocannabinoid system reacts to changes in the body and immediately sets out to restore balance, research carried out by Vallee et al. at the French National Institute of Health and Medical Research (INSERM) shows that the body naturally produces a steroid called pregnenolone in response to high levels of THC.
As mentioned at the beginning of this article, it appears that there is a pretty important functional physiological reason for the body’s synthesis of pregnenolone in response to THC. It has been speculated that the synthesis of pregnenolone in reaction to the presence of high doses of THC is a defense mechanism to prevent us from overdosing on the compound.
The synthesis of pregnenolone to reduce the effects of THC is comparable to the way the endocannabinoid system seeks to maintain homeostasis. By reducing the effects of THC, including the high that it produces, pregnenolone restores the body to a more balanced homeostatic state