Imagine if you had to tell a family that their child was never coming home again...because a driver had a few too many drinks and they were too lazy to get a taxi? How would you feel if it was your child? Your brother, your parent, your best friend? Now imagine that you're the one who had a few drinks and thought...Home isn't too far. I'll make it without getting busted. While on the back streets worrying if the booze bus will catch you, you hit someone. How do you live with that for the rest of your life?Subtle but pervasive changes can occur between uses.
Understanding THC’s interaction with the brain’s important natural cannabinoid chemistry and physiology will now make sense of the impact that overly frequent cannabis use has on the brain and mental functioning.
Because THC stimulates our brain’s natural cannabinoid receptors (CB1) far more strongly and longer than the endogenous cannabinoid neurotransmitters anandamide and 2-AG, cannabis use throws brain chemistry out of balance temporarily, usually to people’s enjoyment. This loss of chemical equilibrium lasts an average of 4 hours when cannabis is inhaled and 8 hours when ingested orally before the liver metabolizes the THC and it is eliminated in the feces (55%) and urine (20%).
Most occasional cannabis users feel little or no effect the following day, but an interesting experiment reveals a subtle impact 24 hours after smoking a single joint. Private licensed pilots with over 200 hours of flight experience had their baseline skills measured in a flight simulator, then were provided a joint containing 10 or 20 mgs of THC to smoke. This was considered the equivalent of a moderate social dose in the mid-1980s.
A variety of pilot actions during routine landings were impaired 24 hours after smoking the joint, including the number and size of adjustments to stabilize the plane, distance off center on landing, and vertical and lateral deviation on approach to landing. Pilots showed no awareness of these impairments. Performance returned to baseline 48 hours after being high.
When the task became more complex by introducing turbulent weather conditions calling on pilots to react in real time to avoid trouble, responses were slower and less well organized than their baseline performance. In other words, the pilots’ response to novel events was altered (see the post How Cannabis Makes Everything So Interesting for clarification on the role our internal cannabinoid system plays in the experience of novelty.)
When THC stimulates CB1 receptors in the amygdala, cannabinoid tone increases, lowering the bar for any stimulus being imbued with a sense of novelty. Novelty draws our attention to unexpected stimuli. This phenomenon is largely responsible for cannabis making everything more interesting. But this is not the end of the story.
Whenever neurons containing CB1 receptors are over-stimulated by THC’s stronger and longer activation, a homeostatic response follows in an effort to rebalance the brain. The phrase “over-stimulated” means only that THC’s stimulation of CB1 receptors exceeds normal physiologic levels, leading to greater than normal negative feedback on the neuron’s release of transmitters with each firing. THC quells neuronal activity not by reducing the rate of nerve cell firing, but rather the amount of transmitter released each time the neuron fires.
As a result, neurons immediately react to THC’s over-stimulation by reducing the number of CB1 receptors. This reduction of receptors is called downregulation. A variety of mechanisms, including pulling receptors inside the cell so they are no longer available to be stimulated, begins with a single exposure to cannabis. By downregulating CB1 receptors, neurons partially regain some balance. Fewer receptors reduce the amount of negative feedback produced by cannabinoid stimulation and a more physiologic balance is re-established.
After THC has been metabolized and eliminated, CB1 receptors begin upregulating back to their normal level of availability. Upregulation after a single or occasional dose of cannabis occurs rapidly. Most people feel unaffected the following day.
