It’s high time that Colorado College students started caring about their brain chemistry as much as their ski waxes. Our brains are brilliant: they got us into CC and they will take us so much further—if we take care of them. Welcome to Campus Pharmacologist, where each week I will explain what is going on in the brain during many common CC activities, ranging from sleep deprivation to illicit drug-use.
Disclaimer: I am in no way encouraging substance-use, but we all know that CC students are a curious group of kids, restrained by few laws. Curiosity is a wonderful thing; it led to the discovery of the Americas, the theory of evolution, and modern medicine. However, curiosity also killed the cat. I am presenting the current scientific facts about pharmacological activities so you can make an informed decision before you conduct a single-subject experiment on your personal neurochemistry.
Let’s start with a Colorado classic: marijuana (Cannabis sativa). The psychoactive ingredient is delta-9 tetrahydrocannabinol (THC), the highest concentration of which is found in the flower bud of the female plants. Typically dried and smoked, airborne THC slips into the lung capillaries and through the blood-brain barrier.
The THC molecule is nonpolar, meaning it is oily when liquefied and therefore dissolves easily in fat but is repelled by water. Since our bodies are mostly fat, they happily absorb the THC and allow it to play in our electrical brain circuits, our neurons. For this reason, it does not take much marijuana to get the inexperienced user high, and it will hit like a train in a matter of seconds.
In our neurons, THC acts on our cannabinoid receptors, which are typically the target of endocannabinoids, molecules similar to THC that occur naturally within our brains. Endocannabinoids are involved in pain, mood, and appetite regulation, as well as memory formation, so there are lots of cannabinoid receptors in these circuits.
We are going to focus on the CB1 cannabinoid receptor, the launch site for THC’s psychoactive effect. Simply, THC is a depressant; it suppresses the function of neurons and neural circuits. After the puff-puff-pass, stimulation must be increased or repeated to produce a neuronal response, especially in the cannabinoid-heavy circuits mentioned above.
For the scientifically inclined, here is the neurochemical mechanism: a neuron with an activated cannabinoid receptor (by either THC or an endocannabinoid) communicates backwards, going against the flow of typical neuron signaling. It causes the upstream neuron to both close its calcium channels and open its potassium channels. It is then very difficult for the neuron to release neurotransmitters that could act on the downstream neuron. Activation of CB1 receptors essentially stops any signals from reaching the original neuron, excitatory, inhibitory, whatever. And the scientist yelled, “SCIENCE!”
In this way THC suppresses entire neuronal circuits. But this suppression has very different effects depending on what exactly is being suppressed. For example, the hypothalamus is in charge of the four Fs: fighting, fleeing, feeding, and mating. Typically, the hypothalamus manages the penultimate F by suppressing appetite. When your blood sugar is low, the hypothalamus inhibits this suppression signal, allowing hunger to reach your consciousness.
Marijuana has this same effect without the drop in blood glucose. THC inhibits the neuron that is suppressing your appetite, so you get hungry and do not stop feeling hungry, irrelevant to how many “dino-nuggets” you consume.
The acute effects of marijuana on general functions are well documented; THC depresses learning, memory, and executive functions while increasing confusion/bewilderment (technical term). Many people also report feeling anxious while high, while some users have no such symptoms. There is evidence that anxiety level is correlated with the user’s expectations; those who expect greater impairment from THC tend to be more anxious.
The effects of consistent, long-term use are similar but not restricted to post-inhalation: deficits in learning, memory, and decision-making, especially reward/punishment analysis in gambling experiments. However, these effects may wear off after a month of sobriety. A study by Pope and colleagues found that the differences in word recall between heavy marijuana users and non-users were no longer significant after not using for 28 days.
There is little physiological evidence for addiction to marijuana, but many people have reported psychological dependence related to THC’s depressant effects.
I would like to dedicate this column to my roommates, my inspiration.
References and further reading:
Basavarajappa, Balapal S. “Neuropharmacology of the Endocannabinoid Signaling System-Molecular Mechanisms, Biological Actions and Synaptic Plasticity.” Current Neuropharmacology 5.2 (2007): 81-97.
Breivogel, Chris S., and Laura J. Sim-Selley. “Basic Neuroanatomy and Neuropharmacology of Cannabinoids.” International Review Of Psychiatry 21.2 (2009): 113-121.
Pope H. G., Jr, A. J. Gruber, J. I. Hudson, M. A. Huestis, and D. Yurgelun-Todd. “Neuropsychological Performance in Long-term Cannabis Users.” Archive of General Psychiatry 58 (2001): 909-915.