Culturally, cannabis is known as a substance that heightens the senses; musicians and concert-goers often use cannabis to increase sensitivity to music, and anyone who has experienced “the munchies” can attest to a heightened sense of taste. For a long time we’ve known that our body’s own endocannabinoid system plays a significant role in eyesight. This phenomenon is less discussed, but none-the-less very real, with cannabinoid receptor agonists (like cannabis) and antagonists (like Rimonabant) both causing changes in eyesight. In fact, injections of antagonists into the eye have been observed to lead to unstable and incorrect retinofugal projection, which is essentially the connection between the optic nerve and the brain. Clearly cannabinoid receptors play an essential role in vision. Of course, this is not very surprising to researchers who understand the layout of the endocannabinoid system. Type 1 cannabinoid receptors (CB1 receptors) are “highly expressed in many structures involved in the processing of visual information”, such as the retina, superior colliculus, lateral geniculate nucleus, and most importantly, the primary visual cortex.

To date, most studies involving the endocannabinoid system and eyesight occur during development phases rather than adult organisms. As a result, researchers from the University of Montreal created a new study to establish the differences in vision between adult mice with cannabinoid receptors and those without (specifically CB1 receptors). To create adult mice without CB1 receptors, researchers deleted the CB1 gene from the mouse DNA before birth. This procedure is known as creating “knockout” mice. In this particular study, 21 knockout mice and 13 normally developing mice were used. The final goal was to submit both groups of mice to several neural-visual tests and determine how vision without CB1 receptors is affected.

Because directly imaging the brain in real time is difficult, researchers had to resort to surgical methods. In this case, researchers put the rodents to sleep first and then cut holes in the rodent scalps over the area of the brain that controls vision. From there, researchers glued imaging chambers onto the rodent skulls directly over the holes so that they could literally scan the brain with no interference in real time. Due to this complexity, special care was given to monitor rodents’ vital signs during the experiments. After the experiments, the rodents were then euthanized chemically. Although the mouse brain is different from the human brain, this type of experiment would obviously never be performed on humans, and enough similarities exist between human and rodent vision that the results should show a high degree of similarity.

From there, the basic procedure involved placing the rodents in a screening chamber, where they were made to face a small digital screen flashing different patterns. To generate basic visual response maps, white horizontal and vertical bars moved over a black background. Afterwards, to examine visual contrast and “selectivity to spatial frequency”, sine waves were made to flow across the screen in different angles. Spatial frequency is simply the level of detail observed per degree of visual angle, or in other words, how much detail the rodents are seeing in each section of their total vision. For the contrast studies, the sine waves were displayed at various contrasts (by varying the difference between the brightest and darkest parts of the screen), while for the spatial frequency studies, the sine waves were displayed at various frequencies (which effectively changed the shape of the waves). From here, cameras in the imaging chambers on the rodents’ skulls recorded images four times a second as the rodents viewed the changing screen patterns. This gave researchers live feedback of the rodents’ visual brain signals in response to the patterns being displayed and therefore an objective means of comparing the two groups’ vision.

After crunching all the data, several large differences existed. For one, CB1 receptor knockout mice had a smaller ovality index, which means that a smaller area of the visual brain was activated. Additional testing confirmed that the total magnitude of visual signal in both groups of mice was roughly the same, which would suggest that the raw data the brains receive is basically the same, but with differences in processing that data. So how does that translate into affecting the visual field? After more testing and signal comparison, researchers determined that the loss is occurring around the peripheral edges of vision. So specifically, CB1 receptor knockout mice have a smaller angle of vision and are less able to see movement at the edges of their field of view.

However, losses did not just occur over the range of vision; the quality of that vision was also affected. CB1 receptor knockout mice showed less spatial frequency, with their brains maximum visual activation occurring at lower frequencies than healthy mice. This translates into being able to track fewer objects and observe less detail. Finally, the contrast studies showed some of the largest differences between the two groups, with knockout mice displaying a decreased sensitivity to contrast, especially at lower values of contrast. As the researchers noted, “sensitivity to contrast is one of the most important attributes of the visual system”. In fact, luminous contrast (the total amount of light observed) is the major component of mammalian sight. Color contrast is more of an add-on and does not account for our main visual navigation system. In other words, mice without CB1 receptors have clearly worse vision, with decreased angle of sight, decreased detail, and finally, and perhaps most importantly, decreased contrast. Interestingly enough, all of these differences occurred primarily on the azimuth axis (the axis which horizontally wraps around the visual section of the brain), suggesting that visual maps in the brain are developed in an axis-dependent matter. To put that in simpler terms, as the brain develops its ability to process visual signals, it seems to lay out neurons in a spatially ordered manner.

In short, researchers have reconfirmed that the endocannabinoid system is essential to maximum vision. Of course, how does this relate to cannabis use in healthy adults? As the researchers noted, in terms of vision, there is likely much less difference observed between cannabis users and non-users than between those with and without cannabinoid receptors at all. However, studies have also confirmed that night-vision is increased upon cannabis consumption, a situation where higher sensitivity in contrast is required. Because of this, it is likely that some of the same effects (in regards to contrast, spatial frequency, etc.) will apply in studies comparing cannabis users to non-users. It remains to be seen whether these differences will allow for therapeutic applications of the endocannabinoid system in terms of neural processing of vision, but at this point in time, it seems likely.

 

Works Cited

Reza Abbas Farishta, Celine Robert, Olivier Turcot, et al. (2015) “Impact of CB1 Receptor Deletion on Visual Responses and Organization of Primary Visual Cortex in Adult Mice”. Investigative Opthalmology and Visual Science (2015) 56:7697-7707.